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      Performance of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies in South Africa

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          Abstract

          Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has been identified as the causative agent for causing the clinical syndrome of COVID -19. Accurate detection of SARS-CoV-2 infection is not only important for management of infected individuals but also to break the chain of transmission. South Africa is the current epicenter of SARS-CoV-2 infection in Africa. To optimize the diagnostic algorithm for SARS-CoV-2 in the South African setting, the study aims to evaluate the diagnostic performance of the EUROIMMUN Anti-SARS-CoV-2 assays. This study reported the performance of EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples targeting the recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Samples were collected from 391 individuals who had tested positive for SARS-CoV-2 and 139 SARS CoV-2 negative controls. Samples were stratified by number of days’ post-PCR diagnosis and symptoms. The sensitivity of EUROIMMUN IgG was 64.1% (95% CI: 59.1–69.0%) and 74.3% (95% CI: 69.6–78.6%) for IgA and the specificity was lower for IgA [84.2% (95% CI: 77–89.2%)] than IgG [95.2% (95% CI: 90.8–98.4%)]. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay sensitivity was higher for IgA but low for IgG and improved for both assays in symptomatic individuals and at later timepoints post PCR diagnosis.

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

              Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Project administrationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – review & editing
                Role: Funding acquisitionRole: InvestigationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 June 2021
                2021
                23 June 2021
                : 16
                : 6
                : e0252317
                Affiliations
                [1 ] Department of Immunology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
                [2 ] National Health Laboratory Services, Johannesburg, South Africa
                [3 ] Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
                [4 ] Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
                [5 ] Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South Africa
                [6 ] Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
                [7 ] Divisions of Chemical and System Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
                [8 ] Department of Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
                [9 ] Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
                Consiglio Nazionale delle Ricerche, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-0686-1293
                https://orcid.org/0000-0001-8988-9595
                https://orcid.org/0000-0002-6360-3488
                Article
                PONE-D-21-05484
                10.1371/journal.pone.0252317
                8221517
                34161348
                43db9d40-7dbb-4730-9d3c-085e496b7b43
                © 2021 Gededzha et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 February 2021
                : 13 May 2021
                Page count
                Figures: 0, Tables: 5, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1171455
                Award Recipient :
                WS, OPP1171455, Bill & Melinda Gates, https://www.gatesfoundation.org/Foundation, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Coronaviruses
                SARS coronavirus
                SARS CoV 2
                Biology and life sciences
                Microbiology
                Medical microbiology
                Microbial pathogens
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                Coronaviruses
                SARS coronavirus
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                Medicine and health sciences
                Pathology and laboratory medicine
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                Biology and life sciences
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                Medicine and Health Sciences
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                COVID-19

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