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


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.

SUBMITTER: Shrock E 

PROVIDER: S-EPMC7857405 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Shrock Ellen E   Fujimura Eric E   Kula Tomasz T   Timms Richard T RT   Lee I-Hsiu IH   Leng Yumei Y   Robinson Matthew L ML   Sie Brandon M BM   Li Mamie Z MZ   Chen Yuezhou Y   Logue Jennifer J   Zuiani Adam A   McCulloch Denise D   Lelis Felipe J N FJN   Henson Stephanie S   Monaco Daniel R DR   Travers Meghan M   Habibi Shaghayegh S   Clarke William A WA   Caturegli Patrizio P   Laeyendecker Oliver O   Piechocka-Trocha Alicja A   Li Jonathan Z JZ   Khatri Ashok A   Chu Helen Y HY   Villani Alexandra-Chloé AC   Kays Kyle K   Goldberg Marcia B MB   Hacohen Nir N   Filbin Michael R MR   Yu Xu G XG   Walker Bruce D BD   Wesemann Duane R DR   Larman H Benjamin HB   Lederer James A JA   Elledge Stephen J SJ  

Science (New York, N.Y.) 20200929 6520


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-  ...[more]

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