Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.

Antibodies, Neutralizing / blood Antibody Formation COVID-19 / blood COVID-19 Serological Testing Cross Reactions Cryoelectron Microscopy Epitope Mapping Epitopes / chemistry Female Humans Male Protein Conformation SARS-CoV-2 / immunology Seroconversion Severity of Illness Index

Journal

Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511

Informations de publication

Date de publication:
27 11 2020
Historique:
received: 22 06 2020
accepted: 25 09 2020
pubmed: 1 10 2020
medline: 1 1 2021
entrez: 30 9 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1126/science.abd4250 PMID: 32994364 PMC: PMC7857405
pubmed: 32994364
pii: science.abd4250
doi: 10.1126/science.abd4250
pmc: PMC7857405
pii:
doi:

Substances chimiques

Antibodies, Neutralizing 0
Epitopes 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI139538
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148232
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118633
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK114563
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 201387/Z/16/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U01 AI138318
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007044
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070253
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI092905
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121394
Pays : United States

Investigateurs

Kendall Lavin-Parsons (K)
Blair Parry (B)
Brendan Lilley (B)
Carl Lodenstein (C)
Brenna McKaig (B)
Nicole Charland (N)
Hargun Khanna (H)
Justin Margolin (J)
Anna Gonye (A)
Irena Gushterova (I)
Tom Lasalle (T)
Nihaarika Sharma (N)
Brian C Russo (BC)
Maricarmen Rojas-Lopez (M)
Moshe Sade-Feldman (M)
Kasidet Manakongtreecheep (K)
Jessica Tantivit (J)
Molly Fisher Thomas (MF)
Betelihem A Abayneh (BA)
Patrick Allen (P)
Diane Antille (D)
Katrina Armstrong (K)
Siobhan Boyce (S)
Joan Braley (J)
Karen Branch (K)
Katherine Broderick (K)
Julia Carney (J)
Andrew Chan (A)
Susan Davidson (S)
Michael Dougan (M)
David Drew (D)
Ashley Elliman (A)
Keith Flaherty (K)
Jeanne Flannery (J)
Pamela Forde (P)
Elise Gettings (E)
Amanda Griffin (A)
Sheila Grimmel (S)
Kathleen Grinke (K)
Kathryn Hall (K)
Meg Healy (M)
Deborah Henault (D)
Grace Holland (G)
Chantal Kayitesi (C)
Vlasta LaValle (V)
Yuting Lu (Y)
Sarah Luthern (S)
Jordan Marchewka Schneider (J)
Brittani Martino (B)
Roseann McNamara (R)
Christian Nambu (C)
Susan Nelson (S)
Marjorie Noone (M)
Christine Ommerborn (C)
Lois Chris Pacheco (LC)
Nicole Phan (N)
Falisha A Porto (FA)
Edward Ryan (E)
Kathleen Selleck (K)
Sue Slaughenhaupt (S)
Kimberly Smith Sheppard (KS)
Elizabeth Suschana (E)
Vivine Wilson (V)
Galit Alter (G)
Alejandro Balazs (A)
Julia Bals (J)
Max Barbash (M)
Yannic Bartsch (Y)
Julie Boucau (J)
Josh Chevalier (J)
Fatema Chowdhury (F)
Kevin Einkauf (K)
Jon Fallon (J)
Liz Fedirko (L)
Kelsey Finn (K)
Pilar Garcia-Broncano (P)
Ciputra Hartana (C)
Chenyang Jiang (C)
Paulina Kaplonek (P)
Marshall Karpell (M)
Evan C Lam (EC)
Kristina Lefteri (K)
Xiaodong Lian (X)
Mathias Lichterfeld (M)
Daniel Lingwood (D)
Hang Liu (H)
Jinqing Liu (J)
Natasha Ly (N)
Ashlin Michell (A)
Ilan Millstrom (I)
Noah Miranda (N)
Claire O'Callaghan (C)
Matthew Osborn (M)
Shiv Pillai (S)
Yelizaveta Rassadkina (Y)
Alexandra Reissis (A)
Francis Ruzicka (F)
Kyra Seiger (K)
Libera Sessa (L)
Christianne Sharr (C)
Sally Shin (S)
Nishant Singh (N)
Weiwei Sun (W)
Xiaoming Sun (X)
Hannah Ticheli (H)
Alicja Trocha-Piechocka (A)
Daniel Worrall (D)
Alex Zhu (A)
George Daley (G)
David Golan (D)
Howard Heller (H)
Arlene Sharpe (A)
Nikolaus Jilg (N)
Alex Rosenthal (A)
Colline Wong (C)

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020, American Association for the Advancement of Science.

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Auteurs

Ellen Shrock (E)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-2484-4374

Eric Fujimura (E)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
Chemical Biology Program, Harvard University, Cambridge, MA, USA.
ORCID: 0000-0001-8213-2143

Tomasz Kula (T)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-6458-9833

Richard T Timms (RT)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-7275-597X

I-Hsiu Lee (IH)

Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-7200-7867

Yumei Leng (Y)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-2512-9284

Matthew L Robinson (ML)

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
ORCID: 0000-0003-0376-8560

Brandon M Sie (BM)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-9405-1850

Mamie Z Li (MZ)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-7188-1330

Yuezhou Chen (Y)

Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.

Jennifer Logue (J)

Department of Medicine, University of Washington, Seattle, WA, USA.

Adam Zuiani (A)

Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
ORCID: 0000-0002-2625-6595

Denise McCulloch (D)

Department of Medicine, University of Washington, Seattle, WA, USA.
ORCID: 0000-0001-8755-6105

Felipe J N Lelis (FJN)

Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
ORCID: 0000-0002-3708-3810

Stephanie Henson (S)

Institute for Cell Engineering, Immunology Division, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.

Daniel R Monaco (DR)

Institute for Cell Engineering, Immunology Division, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.

Meghan Travers (M)

Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
ORCID: 0000-0002-0545-2079

Shaghayegh 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.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
ORCID: 0000-0002-5209-9220

William A Clarke (WA)

Division of Clinical Chemistry, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Patrizio Caturegli (P)

Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Oliver Laeyendecker (O)

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Intramural Research, NIAID, NIH, Baltimore, MD, USA.

Alicja Piechocka-Trocha (A)

Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
Howard Hughes Medical Institute, Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-1547-524X

Jonathan Z Li (JZ)

Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
Infectious Disease Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
ORCID: 0000-0001-9914-9662

Ashok Khatri (A)

Endocrine Unit and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-4740-3846

Helen Y Chu (HY)

Department of Medicine, University of Washington, Seattle, WA, USA.

Alexandra-Chloé Villani (AC)

Massachusetts General Hospital Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-7461-0408

Kyle Kays (K)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Marcia B Goldberg (MB)

Center for Bacterial Pathogenesis, Division of Infectious Diseases, Department of Medicine and Microbiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-4266-9733

Nir Hacohen (N)

Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-2349-2656

Michael R Filbin (MR)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0002-2588-7504

Xu G Yu (XG)

Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
Infectious Disease Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-8295-884X

Bruce D Walker (BD)

Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
Howard Hughes Medical Institute, Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Centre for the AIDS Programme of Research in South Africa, Congella, South Africa.
ORCID: 0000-0001-6122-9245

Duane R Wesemann (DR)

Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
ORCID: 0000-0002-6690-944X

H Benjamin Larman (HB)

Institute for Cell Engineering, Immunology Division, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.

James A Lederer (JA)

Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Stephen J Elledge (SJ)

Department of Genetics, Harvard Medical School, Boston, MA, USA. selledge@genetics.med.harvard.edu.
Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
ORCID: 0000-0001-7923-6283

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité active › Production d'anticorps › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Tests immunologiques › Tests sérologiques › Dépistage sérologique de la COVID-19 › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Phénomènes du système immunitaire › Réaction antigène-anticorps › Réactions croisées › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Cartographie d'interactions entre protéines › Cartographie épitopique › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Phénomènes du système immunitaire › Séroconversion › Viral epitope profiling of COVID-19 patients...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Enquêtes de santé › Indicateurs d'état de santé › Acuité des besoins du patient › Indice de gravité de la maladie › Viral epitope profiling of COVID-19 patients...