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      Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease Patients

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      1 , 1 , 1 , , , , , , , , , , , , , , , ,
      Emerging Infectious Diseases
      Centers for Disease Control and Prevention
      Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, coronavirus, viruses, human coronavirus, HCoV, coronavirus disease 2019, COVID-19, antibodies, serologic analysis, spike protein, receptor-binding domain, RBD, nucleocapsid protein, neutralization, ELISA, respiratory infections, zoonoses

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          Abstract

          A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein–specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2–infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2–specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.

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          Most cited references8

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

            Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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              The species Severe acute respiratory syndrome-related coronavirus : classifying 2019-nCoV and naming it SARS-CoV-2

              The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
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                Author and article information

                Journal
                Emerg Infect Dis
                Emerging Infect. Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                July 2020
                : 26
                : 7
                : 1478-1488
                Affiliations
                [1]Erasmus Medical Center, Rotterdam, the Netherlands (N.M.A. Okba, C.H. GeurtsvanKessel, M.M. Lamers, R.S. Sikkema, E. deBruin, F.D. Chandler, C.B.E.M. Reusken, M.P.G. Koopmans, B.L. Haagmans);
                [2]Charité-Universitätsmedizin Berlin, Berlin, Germany (M.A. Müller, V.M. Corman, C. Drosten);
                [3]German Centre for Infection Research, Berlin (M.A. Müller, V.M. Corman, C. Drosten);
                [4]Utrecht University, Utrecht, the Netherlands (W. Li, C. Wang, B.-J. Bosch);
                [5]Université de Paris, Paris, France (Y. Yazdanpanah, Q. Le Hingrat, D. Descamps);
                [6]Hôpital Bichat-Claude Bernard, Paris (Y. Yazdanpanah, Q. Le Hingrat, D. Descamps, N. Houhou-Fidouh);
                [7]RIVM, Bilthoven, the Netherlands (C.B.E.M. Reusken)
                Author notes
                Address for correspondence: N.M.A. Okba or Bart L. Haagmans, Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands; emails: n.okba@ 123456erasmusmc.nl or b.haagmans@ 123456erasmusmc.nl
                Article
                20-0841
                10.3201/eid2607.200841
                7323511
                32267220
                583ea0f5-d81c-4ca7-8b5e-365d7df7f12d
                History
                Categories
                Expedited
                Research
                Research
                Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease 2019 Patients

                Infectious disease & Microbiology
                severe acute respiratory syndrome coronavirus 2,sars-cov-2,coronavirus,viruses,human coronavirus,hcov,coronavirus disease 2019,covid-19,antibodies,serologic analysis,spike protein,receptor-binding domain,rbd,nucleocapsid protein,neutralization,elisa,respiratory infections,zoonoses

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