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Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.
Shrock, Ellen; Fujimura, Eric; Kula, Tomasz; Timms, Richard T; Lee, I-Hsiu; Leng, Yumei; Robinson, Matthew L; Sie, Brandon M; Li, Mamie Z; Chen, Yuezhou; Logue, Jennifer; Zuiani, Adam; McCulloch, Denise; Lelis, Felipe J N; Henson, Stephanie; Monaco, Daniel R; Travers, Meghan; Habibi, Shaghayegh; Clarke, William A; Caturegli, Patrizio; Laeyendecker, Oliver; Piechocka-Trocha, Alicja; Li, Jonathan Z; Khatri, Ashok; Chu, Helen Y; Villani, Alexandra-Chloé; Kays, Kyle; Goldberg, Marcia B; Hacohen, Nir; Filbin, Michael R; Yu, Xu G; Walker, Bruce D; Wesemann, Duane R; Larman, H Benjamin; Lederer, James A; Elledge, Stephen J.
  • Shrock E; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Fujimura E; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Kula T; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Timms RT; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Lee IH; Chemical Biology Program, Harvard University, Cambridge, MA, USA.
  • Leng Y; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Robinson ML; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Sie BM; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Li MZ; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Chen Y; Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Logue J; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Zuiani A; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • McCulloch D; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lelis FJN; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Henson S; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Monaco DR; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Travers M; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
  • Habibi S; Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Clarke WA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Caturegli P; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Laeyendecker O; Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Piechocka-Trocha A; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Li JZ; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Khatri A; Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Chu HY; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Villani AC; Institute for Cell Engineering, Immunology Division, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
  • Kays K; Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Goldberg MB; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Hacohen N; Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Filbin MR; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Yu XG; Division of Clinical Chemistry, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Walker BD; Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Wesemann DR; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Larman HB; Division of Intramural Research, NIAID, NIH, Baltimore, MD, USA.
  • Lederer JA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
  • Elledge SJ; Howard Hughes Medical Institute, Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Science ; 370(6520)2020 11 27.
Article in English | MEDLINE | ID: covidwho-809284
ABSTRACT
Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 coronavirus disease 2019 (COVID-19) patients and 190 pre-COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Preexisting antibodies in controls recognized SARS-CoV-2 ORF1, whereas only COVID-19 patient antibodies primarily recognized spike protein and nucleoprotein. A machine learning model trained on VirScan data predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic was developed from the most discriminatory SARS-CoV-2 peptides. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, weaker antibody responses to prior infections, and higher incidence of cytomegalovirus and herpes simplex virus 1, possibly influenced by demographic covariates. Among hospitalized patients, males produce stronger SARS-CoV-2 antibody responses than females.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / Epitope Mapping / SARS-CoV-2 / COVID-19 / Epitopes Type of study: Diagnostic study / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Female / Humans / Male Language: English Year: 2020 Document Type: Article Affiliation country: Science.abd4250

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / Epitope Mapping / SARS-CoV-2 / COVID-19 / Epitopes Type of study: Diagnostic study / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Female / Humans / Male Language: English Year: 2020 Document Type: Article Affiliation country: Science.abd4250