Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity
Top Cited Papers
Open Access
- 27 November 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 370 (6520), 1058-+
- https://doi.org/10.1126/science.abd4250
Abstract
Understanding humoral responses to SARS-CoV-2 is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 COVID-19 patients and 190 pre-COVID-19 era controls using VirScan revealed over 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Pre-existing antibodies in controls recognized SARS-CoV-2 ORF1, while only COVID-19 patients primarily recognized spike 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 CMV and HSV-1, possibly influenced by demographic covariates. Among hospitalized patients, males make greater SARS-CoV-2 antibody responses than females.Keywords
Funding Information
- National Institutes of Health (AI139538)
- National Cancer Institute (U24)
- MassCPR (No Number)
- MassCPR (No Number)
- MassCPR (No Number)
- U.S. Department of Defense (W81XWH-16-1-0464)
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