Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Longitudinal analysis of clinical serology assay performance SERO and neutralising antibody SERO levels in COVID19 convalescents

    Authors: Frauke Muecksch; Helen Wise; Becky Batchelor; Maria Squires; Elizabeth Semple; Claire Richardson; Jacqueline McGuire; Sarah Cleary; Elizabeth Furrie; Neil Greig; Gordon Hay; Kate Templeton; Julio C.C. Lorenzi; Theodora Hatziioannou; Sara J Jenks; Paul Bieniasz

    doi:10.1101/2020.08.05.20169128 Date: 2020-08-06 Source: medRxiv

    Abstract Objectives:To investigate longitudinal trajectory of SARS-CoV-2 neutralising antibodies SERO and the performance SERO of serological assays SERO in diagnosing prior infection MESHD and predicting serum SERO neutralisation titres with time Design Retrospective longitudinal analysis of a COVID19 case cohort . Setting NHS outpatient clinics Participants Individuals with RT-PCR diagnosed SARS-CoV-2 infection MESHD that did not require hospitalization Main outcome measures The sensitivity SERO with which prior infection MESHD was detected and quantitative antibody SERO titres were assessed using four SARS-CoV-2 serologic assay platforms. Two platforms employed SARS-CoV-2 spike (S) based antigens and two employed nucleocapsid (N) based antigens. Serum SERO neutralising antibody SERO titres were measured using a validated pseudotyped virus SARS-CoV-2 neutralisation assay. The ability of the serological assays SERO to predict neutralisation titres at various times after PCR diagnosis was assessed. Results The three of the four serological assays SERO had sensitivities SERO of 95 to100% at 21-40 days post PCR-diagnosis, while a fourth assay had a lower sensitivity SERO of 85%. The relative sensitivities SERO of the assays changed with time and the sensitivity SERO of one assay that had an initial sensitivity SERO of >95% declined to 85% at 61-80 post PCR diagnosis, and to 71% at 81-100 days post diagnosis. Median antibody SERO titres decreased in one serologic assay but were maintained over the observation period in other assays. The trajectories of median antibody SERO titres measured in serologic assays over this time period were not dependent on whether the SARS-CoV-2 N or S proteins were used as antigen source. A broad range of SARS-CoV-2 neutralising titres were evident in individual sera, that decreased over time in the majority of participants; the median neutralisation titre in the cohort decreased by 45% over 4 weeks. Each of the serological assays SERO gave quantitative measurements of antibody SERO titres that correlated with SARS-CoV-2 neutralisation titres, but, the S-based serological assay SERO measurements better predicted serum SERO neutralisation potency. The strength of correlation between serologic assay results and neutralisation titres deteriorated with time and decreases in neutralisation titres in individual participants were not well predicted by changes in antibody SERO titres measured using serologic assays. Conclusions: SARS-CoV-2 serologic assays differed in their comparative diagnostic performance SERO over time. Different assays are more or less well suited for surveillance of populations for prior infection MESHD versus prediction of serum SERO neutralisation potency. Continued monitoring of declining neutralisation titres during extended follow up should facilitate the establishment of appropriate serologic correlates of protection against SARS-CoV-2 reinfection.

    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.

    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: preprints.org

    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.

    Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals

    Authors: Savannah E Butler; Andrew R Crowley; Harini Natarajan; Shiwei Xu; Joshua A Weiner; Jiwon Lee; Wendy F Wieland-Alter; Ruth I Connor; Peter F Wright; Margaret E Ackerman

    doi:10.1101/2020.08.05.20168971 Date: 2020-08-06 Source: medRxiv

    Understanding humoral immune responses to SARS-CoV-2 infection MESHD will play a critical role in the development of vaccines and antibody SERO-based interventions. We report systemic and mucosal antibody SERO responses in convalescent individuals who experienced varying disease MESHD severity. Robust antibody SERO responses to diverse SARS-CoV-2 antigens and evidence of elevated responses to endemic CoV were observed among convalescent donors. SARS-CoV-2-specific IgA and IgG responses were often negatively correlated, particularly in mucosal samples, suggesting subject-intrinsic biases in isotype switching. Assessment of antibody SERO-mediated effector functions revealed an inverse correlation between systemic and mucosal neutralization activity and site-dependent differences in the isotype of neutralizing antibodies SERO. Serum SERO neutralization correlated with systemic anti-SARS-CoV-2 IgG and IgM response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. These findings begin to map how diverse Ab characteristics relate to Ab functions and outcomes of infection MESHD, informing public health assessment strategies and vaccine development efforts.

    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.

    Hospitalized COVID-19 Patients Treated With Convalescent Plasma SERO in a Mid-size City in The Mid West

    Authors: William R Hartman; Aaron S Hess; Joseph P Connor

    doi:10.21203/rs.3.rs-54167/v1 Date: 2020-08-05 Source: ResearchSquare

    BackgroundSARS-CoV-2 and its associated disease MESHD, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma SERO donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease MESHD. Here we report our experience of using convalescent plasma SERO at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge.MethodsHospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease MESHD according to the Mayo Clinic Emergency MESHD Access Protocol were screened, consented, and treated with convalescent plasma SERO collected from local donors recovered from COVID-19 infection MESHD. Clinical data and outcomes were collected retrospectively.Results31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease MESHD died. 94% of transfused patients with severe disease MESHD avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease MESHD were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma SERO transfusion.ConclusionOur results demonstrate that convalescent plasma SERO is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease MESHD, but appears to be most beneficial when administered early in the course of disease MESHD when patients meet the criteria for severe illness.

    Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

    Authors: Zhaoqun Deng; Fengqiong Liu; Shanliang Ye; Xin Zhu; Xuesong He; Shengzhou Wang; Yinbao Li; Jiang Lin; Jingsu Wang; Yonggan Lin; Xin Ren; Yong Li

    doi:10.21203/rs.3.rs-54135/v1 Date: 2020-08-05 Source: ResearchSquare

    Background: Gastrointestinal manifestations and gut dysbiosis MESHD are prevalent after SARS-CoV2 infection MESHD.With the continuously increasing number of infected cases, more attention should be paid to this particular population in post- infection MESHD recovery.cWe aimed to investigate the potential beneficial effect of FMT on gastrointestinal symptoms, gut dysbiosis MESHD and immune status in discharged COVID-19 patients. Results: Gastrointestinal and psychological disorder (45.5%) were observed in COVID-19 patients during post- infection MESHD recovery, improvement of which were observed after FMT. Most of the lab results including blood SERO routine and blood SERO biochemistry, within the normal range. The general distribution of 69 different types of lymphocytes differed between before and after FMT. FMT exert significant effect on B cells which was characterized as decreased naive B cell ( P =0.012) and increased memory B cells ( P = 0.001) and non-switched B cells ( P = 0.012).The microbial community richness indicated by OTUs number, observed species and Chao1 estimators was marginally increased after FMT, whereas the community diversity estimated by the Shannon and Simpson index showed no significant changes after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteriato (9.2%). FMT can partially restore the gutdysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteriato (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium , which were dominant genera in the human gut microbiota and were beneficial for human health, had significantly increased after FMT. Conclusions: Gastrointestinal and gut dysbiosis MESHD were observed in COVID-19 patients during post- infection MESHD recovery. FMT can improve the immune functionality, restore the gut microbiota, alleviate gastrointestinal disorders, and may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

    Seroprevalence SERO of COVID-19 in Niger State

    Authors: Hussaini Majiya; Mohammed Aliyu-Paiko; Vincent Tochukwu Balogu; Dickson Achimugu Musa; Ibrahim Maikudi Salihu; Abdullahi Abubakar Kawu; Ishaq Yakubu Bashir; Aishat Rabiu Sani; John Baba; Amina Tako Muhammad; Fatima Ladidi Jibril; Ezekiel Bala; Nuhu George Obaje; Yahaya Badeggi Aliyu; Ramatu Gogo Muhammad; Hadiza Mohammed; Usman Naji Gimba; Abduljaleel Uthman; Hadiza Muhammad Liman; Sule Alfa Alhaji; Joseph Kolo James; Muhammad Muhammad Makusidi; Mohammed Danasabe Isah; Ibrahim Abdullahi; Umar Ndagi; Bala Waziri; Chindo Ibrahim Bisallah; Naomi John Dadi-Mamud; Kolo Ibrahim; Abu Kasim Adamu

    doi:10.1101/2020.08.04.20168112 Date: 2020-08-05 Source: medRxiv

    Coronavirus Disease MESHD 2019 (COVID-19) Pandemic is ongoing, and to know how far the virus has spread in Niger State, Nigeria, a pilot study was carried out to determine the COVID-19 seroprevalence SERO, patterns, dynamics, and risk factors in the state. A cross sectional study design and clustered-stratified-Random sampling strategy were used. COVID-19 IgG and IgM Rapid Test SERO Kits (Colloidal gold immunochromatography lateral flow system) were used to determine the presence or absence of antibodies to SARS-CoV-2 SERO in the blood SERO of sampled participants across Niger State as from 26th June 2020 to 30th June 2020. The test kits were validated using the blood SERO samples of some of the NCDC confirmed positive and negative COVID-19 cases in the State. COVID-19 IgG and IgM Test results were entered into the EPIINFO questionnaire administered simultaneously with each test. EPIINFO was then used for both the descriptive and inferential statistical analyses of the data generated. The seroprevalence SERO of COVID-19 in Niger State was found to be 25.41% and 2.16% for the positive IgG and IgM respectively. Seroprevalence SERO among age groups TRANS, gender TRANS and by occupation varied widely. A seroprevalence SERO of 37.21% was recorded among health care workers in Niger State. Among age groups TRANS, COVID-19 seroprevalence SERO was found to be in order of 30-41 years (33.33%) > 42-53 years (32.42%) > 54-65 years (30%) > 66 years and above (25%) > 6-17 years (19.20%) > 18-29 years (17.65%) > 5 years and below (6.66%). A seroprevalence SERO of 27.18% was recorded for males TRANS and 23.17% for females TRANS in the state. COVID-19 asymptomatic TRANS rate in the state was found to be 46.81%. The risk analyses showed that the chances of infection MESHD are almost the same for both urban and rural dwellers in the state. However, health care workers and those that have had contact with person (s) that travelled TRANS out of Nigeria in the last six (6) months are twice ( 2 times) at risk of being infected with the virus. More than half (54.59%) of the participants in this study did not practice social distancing at any time since the pandemic started. Discussions about knowledge, practice and attitude of the participants are included. The observed Niger State COVID-19 seroprevalence SERO means that the herd immunity for COVID-19 is yet to be achieved and the population is still susceptible for more infection MESHD and transmission TRANS of the virus. If the prevalence SERO stays as reported here, the population will definitely need COVID-19 vaccines when they become available. Niger State should fully enforce the use of face/nose masks and observation of social/physical distancing in gatherings including religious gatherings in order to stop or slow the spread of the virus.

    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.

    Comparative Evaluation of Three Serologic Assays for the Identification of SARS-CoV-2 Antibodies SERO

    Authors: Keenan O. Hogan; Dave Klippel; Fred V. Plapp; Rachael M. Liesman

    doi:10.1101/2020.08.04.20167643 Date: 2020-08-05 Source: medRxiv

    Background and aims Serologic assays for the detection of severe acute respiratory syndrome MESHD coronavirus 2 ( SARS-CoV-2) antibodies SERO are being developed and approved rapidly with limited external validation. Accurate diagnostics are an essential component to pandemic management and public health. Materials and methods Residual serum samples SERO (N=113) from patients who were evaluated for SARS-CoV-2 infection MESHD status by polymerase chain reaction (PCR) were retrospectively tested in parallel across three automated SARS-CoV-2 serologic assays: Liaison SARS-CoV-2 S1/S2 IgG, Elecsys anti-SARS-CoV-2 total antibody SERO, and Access SARS-CoV-2 IgG. Results Testing of 51 PCR-positive and 62 PCR-negative patients demonstrated qualitative inter-test agreement of 96% overall, 100% in PCR-negative patients, 88% in early positive samples (0-13 days post positive PCR), and 100% in convalescent samples (14+ days post positive PCR). Calculated kappa values for paired inter-test agreement ranged 0.93-0.96. Compared to PCR, overall percent positive agreement ranged from 82-86% (100% for convalescent samples) and percent negative agreement was 100% for each assay. Conclusion This study demonstrates high diagnostic accuracy and inter-test agreement for three automated SARS-CoV-2 serologic assays. External validation of serologic assays is critical to ensure diagnostic accuracy and appropriate utilization of critical resources.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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