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

Ellen Shrock; Eric Fujimura; Tomasz Kula; Richard T Timms; I-Hsiu Lee; Yumei Leng; Matthew L Robinson; Brandon M Sie; Mamie Z Li; Yuezhou Chen; Jennifer Logue; Adam Zuiani; Denise McCulloch; Felipe J N Lelis; Stephanie Henson; Daniel R Monaco; Meghan Travers; Shaghayegh Habibi; William A Clarke; Patrizio Caturegli; Oliver Laeyendecker; Alicja Piechocka-Trocha; Jonathan Z Li; Ashok Khatri; Helen Y Chu; MGH COVID-19 Collection & Processing Team; Alexandra-Chloé Villani; Kyle Kays; Marcia B Goldberg; Nir Hacohen; Michael R Filbin; Xu G Yu; Bruce D Walker; Duane R Wesemann; H Benjamin Larman; James A Lederer; Stephen J Elledge

doi:10.1126/science.abd4250

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

Science. 2020 Nov 27;370(6520):eabd4250. doi: 10.1126/science.abd4250. Epub 2020 Sep 29.

Authors

Ellen Shrock^#^{1

2}, Eric Fujimura^#^{1

2

3}, Tomasz Kula^#^{1

2}, Richard T Timms^#^{1

2}, I-Hsiu Lee⁴, Yumei Leng^{1

2}, Matthew L Robinson⁵, Brandon M Sie^{1

2}, Mamie Z Li^{1

2}, Yuezhou Chen^{6

7}, Jennifer Logue⁸, Adam Zuiani^{6

7}, Denise McCulloch⁸, Felipe J N Lelis^{6

7}, Stephanie Henson⁹, Daniel R Monaco⁹, Meghan Travers^{6

7}, Shaghayegh Habibi^{6

7}, William A Clarke¹⁰, Patrizio Caturegli¹¹, Oliver Laeyendecker^{5

12}, Alicja Piechocka-Trocha^{7

13}, Jonathan Z Li^{7

14}, Ashok Khatri¹⁵, Helen Y Chu⁸; MGH COVID-19 Collection & Processing Team; Alexandra-Chloé Villani¹⁶, Kyle Kays¹⁷, Marcia B Goldberg¹⁸, Nir Hacohen¹⁹, Michael R Filbin¹⁷, Xu G Yu^{7

14

20

21}, Bruce D Walker^{7

13

22}, Duane R Wesemann^{6

7}, H Benjamin Larman⁹, James A Lederer²³, Stephen J Elledge^{24

2

7}

Collaborators

MGH COVID-19 Collection & Processing Team:
Kendall Lavin-Parsons, Blair Parry, Brendan Lilley, Carl Lodenstein, Brenna McKaig, Nicole Charland, Hargun Khanna, Justin Margolin, Anna Gonye, Irena Gushterova, Tom Lasalle, Nihaarika Sharma, Brian C Russo, Maricarmen Rojas-Lopez, Moshe Sade-Feldman, Kasidet Manakongtreecheep, Jessica Tantivit, Molly Fisher Thomas, Betelihem A Abayneh, Patrick Allen, Diane Antille, Katrina Armstrong, Siobhan Boyce, Joan Braley, Karen Branch, Katherine Broderick, Julia Carney, Andrew Chan, Susan Davidson, Michael Dougan, David Drew, Ashley Elliman, Keith Flaherty, Jeanne Flannery, Pamela Forde, Elise Gettings, Amanda Griffin, Sheila Grimmel, Kathleen Grinke, Kathryn Hall, Meg Healy, Deborah Henault, Grace Holland, Chantal Kayitesi, Vlasta LaValle, Yuting Lu, Sarah Luthern, Jordan Marchewka Schneider, Brittani Martino, Roseann McNamara, Christian Nambu, Susan Nelson, Marjorie Noone, Christine Ommerborn, Lois Chris Pacheco, Nicole Phan, Falisha A Porto, Edward Ryan, Kathleen Selleck, Sue Slaughenhaupt, Kimberly Smith Sheppard, Elizabeth Suschana, Vivine Wilson, Galit Alter, Alejandro Balazs, Julia Bals, Max Barbash, Yannic Bartsch, Julie Boucau, Josh Chevalier, Fatema Chowdhury, Kevin Einkauf, Jon Fallon, Liz Fedirko, Kelsey Finn, Pilar Garcia-Broncano, Ciputra Hartana, Chenyang Jiang, Paulina Kaplonek, Marshall Karpell, Evan C Lam, Kristina Lefteri, Xiaodong Lian, Mathias Lichterfeld, Daniel Lingwood, Hang Liu, Jinqing Liu, Natasha Ly, Ashlin Michell, Ilan Millstrom, Noah Miranda, Claire O'Callaghan, Matthew Osborn, Shiv Pillai, Yelizaveta Rassadkina, Alexandra Reissis, Francis Ruzicka, Kyra Seiger, Libera Sessa, Christianne Sharr, Sally Shin, Nishant Singh, Weiwei Sun, Xiaoming Sun, Hannah Ticheli, Alicja Trocha-Piechocka, Daniel Worrall, Alex Zhu, George Daley, David Golan, Howard Heller, Arlene Sharpe, Nikolaus Jilg, Alex Rosenthal, Colline Wong

Affiliations

¹ Department of Genetics, Harvard Medical School, Boston, MA, USA.
² Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Harvard Medical School, Boston, MA, USA.
³ Chemical Biology Program, Harvard University, Cambridge, MA, USA.
⁴ Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Division of Allergy and Immunology and Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA.
⁸ Department of Medicine, University of Washington, Seattle, WA, USA.
⁹ Institute for Cell Engineering, Immunology Division, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
¹⁰ Division of Clinical Chemistry, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹¹ Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹² Division of Intramural Research, NIAID, NIH, Baltimore, MD, USA.
¹³ Howard Hughes Medical Institute, Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
¹⁴ Infectious Disease Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁵ Endocrine Unit and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ Massachusetts General Hospital Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁷ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁸ Center for Bacterial Pathogenesis, Division of Infectious Diseases, Department of Medicine and Microbiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁹ Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, MA, USA.
²⁰ Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
²¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
²² Centre for the AIDS Programme of Research in South Africa, Congella, South Africa.
²³ Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁴ Department of Genetics, Harvard Medical School, Boston, MA, USA. selledge@genetics.med.harvard.edu.

^# Contributed equally.

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.

Publication types

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

MeSH terms

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

Substances

Antibodies, Neutralizing
Epitopes

Abstract

Publication types

MeSH terms

Substances

Grants and funding