Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (34)

Fever (25)

Severe infection (10)

Anosmia (9)

Cough (8)


Transmission

Seroprevalence
    displaying 1 - 10 records in total 605
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    The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody SERO, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody SERO

    Authors: Conrad E. Z Chan; Shirley G.K. Seah; De Hoe Chye; Shane Massey; Maricela Torres; Angeline P.C. Lim; Steven K.K. Wong; Jacklyn J.Y. Neo; Pui San Wong; Jie Hui Lim; Gary S.L. Loh; Dong Ling Wang; Jerome D. Boyd-Kirkup; Siyu Guan; Dipti Thakkar; Guo Hui Teo; Kiren Purushotorman; Paul E. Hutchinson; Barnaby Young; David Chien Boon Lye; Jenny G. Low; Paul A. MacAry; Hannes Hentze; Venkateshan S. Prativadibhayankara; Kantharaj Ethirajulu; Jason Comer; Chien-Te K. Tseng; Alan D.T. Barrett; Piers J. Ingram; Trevor Brasel; Brendon J. Hanson

    doi:10.1101/2020.10.26.355107 Date: 2020-10-26 Source: bioRxiv

    SARS-CoV-2-neutralizing antibodies SERO are promising therapeutics for COVID-19. However, little is known about the mechanisms of action of these antibodies SERO or their effective dosing windows. We report the discovery and development of SC31, a potent SARS-CoV-2 neutralizing IgG1 antibody SERO, originally isolated from a convalescent patient at day 27 after the onset of symptoms TRANS. Neutralization occurs via a binding epitope that maps within the ACE2 interface of the SARS-CoV-2 Spike protein, conserved across all common circulating SARS-CoV-2 mutants. In SARS-CoV-2 infected MESHD K18-human ACE2 transgenic mice, SC31 demonstrated potent survival benefit by dramatically reducing viral load concomitant with attenuated pro-inflammatory responses linked to severe systemic disease MESHD, such as IL-6. Comparison with a Fc-null LALA variant of SC31 demonstrated that optimal therapeutic efficacy of SC31 requires intact Fc-mediated effector functions that can further induce an IFN{gamma}-driven anti-viral immune response. Dose-dependent efficacy for SC31 was observed down to 5mg/kg when dosed before the activation of lung inflammatory responses. Importantly, despite Fc{gamma}R binding, no evidence of antibody SERO dependent enhancement was observed with the Fc-competent SC31 even at sub-therapeutic doses. Therapeutic efficacy was confirmed in SARS-CoV-2-infected MESHD hamsters, where SC31 again significantly reduced viral load, decreased lung lesions MESHD and inhibited progression to severe disease manifestations. This study underlines the potential for significant COVID-19 patient benefit for the SC31 antibody SERO that justifies rapid advancement to the clinic, as well as highlighting the importance of appropriate mechanistic and functional studies during development.

    Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody SERO

    Authors: Ronit Rosenfeld; Tal Noy-Porat; Adva Mechaly; Efi Makdasi; Yinon Levy; Ron Alcalay; Reut Falach; Moshe Aftalion; Eyal Epstein; David Gur; Theodor Chitlaru; Einat B. Vitner; Sharon Melamed; Boaz Politi; Ayelet Zauberman; Shirley Lazar; Yentl Evgy; Shmuel Yitzhaki; Shmuel C. Shapira; Tomer Israely; Ohad Mazor; Paul A. MacAry; Hannes Hentze; Venkateshan S. Prativadibhayankara; Kantharaj Ethirajulu; Jason Comer; Chien-Te K. Tseng; Alan D.T. Barrett; Piers J. Ingram; Trevor Brasel; Brendon J. Hanson

    doi:10.1101/2020.10.26.354811 Date: 2020-10-26 Source: bioRxiv

    Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human live, sociality and global economy. Neutralizing antibodies SERO constitute a highly promising approach for treating and preventing infection MESHD by this novel pathogen. In the present study, we characterized and further evaluated the recently identified human monoclonal MD65 antibody SERO for its ability to provide protection against a lethal SARS-CoV-2 infection MESHD of K18-hACE2 transgenic mice. 75% of the untreated mice succumbed 6-9 days post-infection while administration of the MD65 antibody SERO as late as 3 days after exposure, rescued all infected animals. The data unprecedentedly demonstrate, the therapeutic value of human monoclonal antibodies SERO as a life-saving treatment of severe COVID-19 infection MESHD.

    Clinical correlations of SARS-CoV-2 antibody SERO responses in patients with COVID-19 infection MESHD

    Authors: Mia DeSimone; Daimon P Simmons; Nicole Tolan; Stacy Melanson; Athena Petrides; Milenko Tanasijevic; Peter Schur; Jill Hakim; Keirstinne Turcios; Lee Atkinson-McEvoy; Raphael Hirsch; Roberta L Keller; Theodore Ruel; Auritte Cohen-Ross; Araceli Leon; Naomi Bardach; Aaron F Carlin; Alex E. Clark; Laura Berreta; Daniel Maneval; Felix Frueh; Brett L Hurst; Hong Wang; Klaudia I Kocurek; Frank M Raushel; Jair L. Siqueira-Neto; Thomas D Meek; James H McKerrow

    doi:10.1101/2020.10.22.20213207 Date: 2020-10-23 Source: medRxiv

    Coronavirus disease 19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). Understanding the clinical correlations of antibodies SERO produced by infected individuals will be critical for incorporating antibody SERO results into clinical management. This study was an observational cohort study to evaluate antibody SERO responses in individuals with PCR-confirmed COVID-19, including 48 hospitalized patients diagnosed with COVID-19 by real-time polymerase chain reaction (RT-PCR) at a large tertiary care medical center. Serum samples SERO were obtained from patients at various time points during the disease course and tested for IgM and IgG antibodies SERO against SARS-CoV-2. Medical records were reviewed, and antibody SERO levels were compared with clinical and laboratory findings. Patients did not have high levels of antibodies SERO within one week of symptoms, but most had detectable IgM and IgG antibodies SERO between 8 and 29 days after onset of symptoms TRANS. Some individuals did not develop measurable levels of IgM or IgG antibodies SERO. IgM antibodies SERO were associated with elevated ALT, but there were no other significant associations. We did not observe significant associations of SARS-CoV-2 antibodies SERO with clinical outcomes, including intubation and death MESHD. SARS-CoV-2 IgM MESHD IgM and IgG antibodies SERO were unlikely to be detected in the first week of infection or in severely HP infection or in severely MESHD immunocompromised individuals. Although we did not observe associations with clinical outcomes, IgM antibodies SERO were associated with higher ALT levels. Antibody SERO production reflects the virus-specific immune response, which is important for immunity but also drives pathology, and antibody SERO levels may be important for guiding treatment of individuals with COVID-19.

    Emergency Response for Evaluating SARS-CoV-2 Immune Status, Seroprevalence SERO and Convalescent Plasma SERO in Argentina

    Authors: Diego Ojeda; Maria Mora Gonzalez Lopez Ledesma; Horacio Palleres; Guadalupe Costa Navarro; Lautaro Sanchez; Beatriz Perazzi; Sergio Villordo; Diego Alvarez; - BioBanco Working Group; Marcela Echavarria; Kasopefoluwa Y. Oguntuyo; Christian Stevens; Benhur Lee; Jorge Carradori; Julio Caramelo; Marcelo Yanovsky; Andrea Gamarnik; Bart N Lambrecht; Lynda Coughlan; Adolfo Garcia-Sastre; Bruno G De Geest; Michael Schotsaert; Marion Yger; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.21.20216960 Date: 2020-10-23 Source: medRxiv

    We report the emergency development and application of a robust serologic test SERO to evaluate acute and convalescent antibody SERO responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay SERO ( ELISA SERO) plate. Over half million tests have already been distributed to detect and quantify antibodies SERO for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence SERO studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic TRANS detection and policy making in the country. Analysis of antibody SERO levels and longitudinal studies of symptomatic and asymptomatic TRANS SARS-CoV-2 infections MESHD in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset TRANS, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic TRANS cases showed a wide range of antibody SERO responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma SERO applications, a protocol was standardized for the assessment of end point IgG antibody SERO titers with COVIDAR with more than 500 plasma SERO donors. The protocol showed a positive correlation with neutralizing antibody SERO titers, and was used to assess antibody SERO titers for clinical trials and therapies across the country. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody SERO kinetics in infected individuals and mitigation policies to cope with pandemic needs.

    SARS-CoV-2 antibodies SERO in the Southern Region of New Zealand, 2020

    Authors: Alyson Craigie; Reuben McGregor; Alana Whitcombe; Lauren Carlton; David Harte; Michelle Sutherland; Matthew Parry; Erasmus Smit; Gary McAuliffe; James Ussher; Nicole Moreland; Susan Jack; Arlo Upton; Danielle Skinner; Ken Hirata; Sungjun Beck; Aaron F Carlin; Alex E. Clark; Laura Berreta; Daniel Maneval; Felix Frueh; Brett L Hurst; Hong Wang; Klaudia I Kocurek; Frank M Raushel; Jair L. Siqueira-Neto; Thomas D Meek; James H McKerrow

    doi:10.1101/2020.10.20.20215616 Date: 2020-10-23 Source: medRxiv

    Background: During New Zealand's first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection MESHD rate. PCR testing was initially limited by a narrow case definition and limited laboratory capacity, so cases may have been missed. Objectives: To evaluate the Abbott SARS-CoV-2 MESHD IgG nucleocapsid assay, alongside spike-based assays, and to determine the frequency of antibodies SERO among PCR-confirmed and probable cases, contacts, and higher risk individuals in the Southern Region of NZ. Study design: Pre-pandemic sera (n=300) were used to establish assay specificity and sera from PCR-confirmed SARS-CoV-2 patients (n=78) to establish sensitivity SERO. For prevalence SERO analysis, all samples (n=1214) were tested on the Abbott assay, and all PCR- confirmed cases TRANS (n=78), probable cases (n=9), and higher risk individuals with grey-zone (n=14) or positive results (n=11) were tested on four additional SARS-CoV-2 serological assays SERO. Results: The median time from infection MESHD onset to serum SERO collection for PCR- confirmed cases TRANS was 14 weeks (range 11-17 weeks). The Abbott assay demonstrated a specificity of 99.7% (95% CI, 98.2%-99.99%) and a sensitivity SERO of 76.9% (95% CI, 66.0%-85.7%). Spike-based assays demonstrated superior sensitivity SERO ranging 89.7-94.9%. Nine previously undiagnosed sero-positive individuals were identified, and all had epidemiological risk factors. Conclusions: Spike-based assays demonstrated higher sensitivity SERO than the Abbott IgG assay, likely due to temporal differences in antibody SERO persistence. No unexpected SARS-CoV-2 infections MESHD were found in the Southern region of NZ, supporting the elimination status of the country at the time this study was conducted.

    Seroprevalence SERO of SARS-CoV-2 IgG antibodies SERO in two regions of Estonia (KoroSero-EST-1)

    Authors: Piia Jogi; Hiie Soeorg; Diana Ingerainen; Mari Soots; Freddy Lattekivi; Paul Naaber; Karolin Toompere; Part Peterson; Liis Haljasmagi; Eva Zusinaite; Hannes Vaas; Merit Pauskar; Arina Shablinskaja; Katrin Kaarna; Heli Paluste; Kai Kisand; Marje Oona; Riina Janno; Irja Lutsar; Raissa Prado Rocha; Alex Fiorini de Carvalho; Pedro Augusto Alves; Jose Luiz Proenca Modena; Artur Torres Cordeiro; Daniela Barreto Barbose Trivella; Rafael Elias Marques; Ronir R Luiz; Paolo Pelosi; Jose Roberto Lapa e Silva

    doi:10.1101/2020.10.21.20216820 Date: 2020-10-23 Source: medRxiv

    Background: In Estonia, during the first wave of COVID-19 total number of cases confirmed TRANS by PCR was 13.3/10,000, similar in most regions, including capital Tallinn, but in the hotspot of Estonian epidemic, an island Saaremaa, the cumulative incidence was 166.1/10,000. Aim: We aimed to determine the prevalence SERO of SARS-CoV-2 IgG antibodies SERO in these two regions, symptoms associated with infection MESHD and factors associated with antibody SERO concentrations. Methods: Participants were selected using stratified (formed by age TRANS decades) random sampling and recruited by general practitioners. IgG were determined from sera by four assays. Symptoms of acute respiratory illness MESHD associated with seropositivity were analyzed by multiple correspondence analysis, antibody SERO concentrations by multiple linear regression. Results: Total of 3608 individual were invited and 1960 recruited From May 8 to July 31, 2020. Seroprevalence SERO was 1.5% (95% confidence interval (CI) 0.9-2.5) and 6.3% (95% CI 5.0-7.9), infection fatality rate 0.1% (95% CI 0.0-0.2) and 1.3% (95% CI 0.4-2.1) in Tallinn and Saaremaa, respectively. Of seropositive subjects 19.2% (14/73) had acute respiratory illness MESHD. Fever HP Fever MESHD, diarrhea HP diarrhea MESHD and the absence of cough HP cough MESHD and runny nose were associated with seropositivity in individuals aged TRANS 50 or more years. IgG concentrations were higher if fever HP fever MESHD, difficulty breathing, shortness of breath MESHD, chest pain HP chest pain MESHD or diarrhea HP diarrhea MESHD was present, or hospitalization required. Conclusion: Similarly to other European countries the seroprevalence SERO of SARS-CoV-2 in Estonia was low even in the hotspot region Saaremaa suggesting that majority of population is still susceptible to SARS-CoV-2. Focusing only on respiratory symptoms may delay accurate diagnosis of SARS-CoV-2 infection MESHD.

    Transferrin receptor is another receptor for SARS-CoV-2 entry

    Authors: Xiaopeng Tang; Mengli Yang; Zilei Duan; Zhiyi Liao; Lei Liu; Ruomei Cheng; Mingqian Fang; Gan Wang; Hongqi Liu; Jingwen Xu; Peter M Kamau; Zhiye Zhang; Lian Yang; Xudong Zhao; Xiaozhong Peng; Ren Lai; Hamida Hammad; Bart N Lambrecht; Lynda Coughlan; Adolfo Garcia-Sastre; Bruno G De Geest; Michael Schotsaert; Marion Yger; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.23.350348 Date: 2020-10-23 Source: bioRxiv

    Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) entry to cause coronavirus disease MESHD 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry MESHD. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect MESHD mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody SERO (EC50 16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry MESHD and a promising anti-COVID-19 target.

    Serological surveillance of SARS-CoV-2: trends and humoral response in a cohort of public health workers

    Authors: Ross J Harris; Heather J Whitaker; Nick J Andrews; Felicity Aiano; Zahin Amin-Chowdhury; Jessica Flood; Ray Borrow; Ezra Linley; Shazaad Ahmad; Lorraine Stapley; Bassam Hallis; Gayatri Amirthalingam; Ben Parker; Alex Horsley; Timothy J G Brooks; Kevin Brown; Mary Ramsay; Shamez Ladhani; Paula Veronica Martini Maciel; Raissa Prado Rocha; Alex Fiorini de Carvalho; Pedro Augusto Alves; Jose Luiz Proenca Modena; Artur Torres Cordeiro; Daniela Barreto Barbose Trivella; Rafael Elias Marques; Ronir R Luiz; Paolo Pelosi; Jose Roberto Lapa e Silva

    doi:10.1101/2020.10.21.20216689 Date: 2020-10-23 Source: medRxiv

    Background There is considerable debate about the rate of antibody SERO waning after SARS-CoV-2 infection MESHD, raising questions around long-term immunity following both natural infection MESHD and vaccination. We undertook prospective serosurveillance in a large cohort of healthy adults TRANS from the start of the epidemic in England. Methods The serosurveillance cohort included office and laboratory-based staff and healthcare workers in 4 sites in England, who were tested monthly for SARS-CoV-2 spike protein and nucleoprotein IgG between 23rd March and 20th August 2020. Antibody SERO levels from 21 days after a positive test were modelled using mixed effects regression models. Findings In total, 2247 individuals were recruited and 2014 (90%) had 3-5 monthly antibody tests SERO. Overall, 272 (12.1%) of individuals had at least one positive/equivocal spike protein IgG result, with the highest proportion in a hospital site (22%), 14% in London and 2.1% in a rural area. Results were similar for nucleoprotein IgG. Following a positive result, 39/587 (6.6%) tested negative for nucleoprotein IgG and 52/515 (10.1%) for spike protein IgG. Nucleoprotein IgG declined by 6.4% per week (95% CI, 5.5-7.4%; half-life, 75 [95% CI, 66-89] days) and spike protein IgG by 5.8% (95% CI, 5.1-6.6%; half-life, 83 [95% CI, 73-96] days). Conclusions Over the study period SARS-CoV-2 seropositivity was 8-10% overall and up to 21% in clinical healthcare workers. In seropositive individuals, nucleoprotein and spike protein IgG antibodies SERO declined with time after infection MESHD and 50% are predicted to fall HP below the positive test threshold after 6 months.

    Broadly-targeted autoreactivity is common in severe SARS-CoV-2 Infection MESHD

    Authors: Matthew Woodruff; Richard P Ramonell; F. Eun-Hyung Lee; Ignacio Sanz; Shafia Rahman; Morayma Reyes Gil; Bryan Greenhouse; Jill Hakim; Keirstinne Turcios; Lee Atkinson-McEvoy; Raphael Hirsch; Roberta L Keller; Theodore Ruel; Auritte Cohen-Ross; Araceli Leon; Naomi Bardach; Aaron F Carlin; Alex E. Clark; Laura Berreta; Daniel Maneval; Felix Frueh; Brett L Hurst; Hong Wang; Klaudia I Kocurek; Frank M Raushel; Jair L. Siqueira-Neto; Thomas D Meek; James H McKerrow

    doi:10.1101/2020.10.21.20216192 Date: 2020-10-23 Source: medRxiv

    Severe SARS-CoV-2 infection is linked to the presence of autoantibodies against multiple targets, including phospholipids and type-I interferons. We recently identified activation of an autoimmune-prone B cell response pathway as correlate of severe COVID-19, raising the possibility of de novo autoreactive antibody SERO production during the antiviral response. Here, we identify autoreactive antibodies SERO as a common feature of severe COVID-19, identifying biomarkers of tolerance breaks that may indicate aggressive immunomodulation.

    mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies SERO and mediates protection in rodents

    Authors: Susanne Rauch; Nicole Roth; Kim Schwendt; Mariola Fotin-Mleczek; Stefan O. Mueller; Benjamin Petsch; Victor Pitron; Salimata Gassama; Sara Sambin; Stephanie Bombois; Bastien Herlin; Gaelle Ouvrard; Gaelle Bruneteau; Adele Hesters; Ana Zenovia Gales; Bruno Millet; Foudil Lamari; Stephane Lehericy; Vincent Navarro; Benjamin Rohaut; Sophie Demeret; Thierry Maisonobe; Marion Yger; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.23.351775 Date: 2020-10-23 Source: bioRxiv

    The devastating SARS-CoV-2 pandemic demands rapid vaccine development and large scale production to meet worldwide needs. mRNA vaccines have emerged as one of the most promising technologies to address this unprecedented challenge. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle (LNP) encapsulated non-modified mRNA vaccine that encodes the full length, pre-fusion stabilised SARS-CoV-2 Spike MESHD (S) protein. S translated from CVnCoV is cleaved, post-translationally modified, and presented on the cell surface, highlighting the ability of mRNA vaccines to mimic antigen presentation during viral infection MESHD. Immunisation with CVnCoV induced strong humoral responses with high titres of virus neutralizing antibodies SERO in mice and hamsters and robust CD4+ and CD8+ T cell responses in mice. Most importantly, vaccination with CVnCoV fully protected hamster lungs from challenge with wild type SARS-CoV-2. To gain insights in the risk of vaccine-enhanced disease, hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication were analysed for signs of vaccine-enhanced disease. No evidence of increased viral replication or exacerbated inflammation MESHD and damage to viral target organs was detectable, giving strong evidence for a favourable safety profile of CVnCoV. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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