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

2020; American Association for the Advancement of Science; Volume: 370; Issue: 6520 Linguagem: Inglês

10.1126/science.abd4250

1095-9203

Ellen Shrock, Eric Fujimura, Tomasz Kula, Richard T. Timms, I‐Hsiu Lee, Yumei Leng, Matthew L. Robinson, Brandon Sie, Mamie Z. Li, Yuezhou Chen, Jennifer K. Logue, Adam Zuiani, Denise J. McCulloch, Felipe Lelis, Stephanie Henson, Daniel R. Monaco, Meghan Travers, Shaghayegh Habibi, William Clarke, Patrizio Caturegli, Oliver Laeyendecker, Alicja Piechocka‐Trocha, Jonathan Z. Li, Ashok Khatri, Helen Y. Chu, Alexandra–Chloé Villani, Kyle R. Kays, Marcia B. Goldberg, Nir Hacohen, Michael R. Filbin, Xu G. Yu, Bruce D. Walker, Duane R. Wesemann, H. Benjamin Larman, Eddie A. James, Stephen J. Elledge, Kendall M. Lavin-Parsons, Blair A. Parry, Brendan M. Lilley, Carl L. Lodenstein, Brenna McKaig, Nicole C. Charland, Hargun K. Khanna, Justin Margolin, Anna L.K. Gonye, Irena Gushterova, Thomas J. LaSalle, Nihaarika Sharma, Brian C. Russo, Maricarmen Rojas-López, Moshe Sade-Feldman, Kasidet Manakongtreecheep, Jessica Tantivit, Molly Thomas, Betelihem A. Abayneh, Patrick Allen, Diane Antille, Katrina Armstrong, Siobhan Boyce, Joan Braley, Kelley R. Branch, Katherine Broderick, Julia Carney, Andrew Chan, Susan Davidson, Michael Dougan, David Drew, Ashley Elliman, Keith T. Flaherty, Jeanne Flannery, Pamela J. 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, Brittani Martino, Roseann McNamara, Christian Nambu, Susan C. Nelson, Marjorie Noone, Christine Ommerborn, Lois Chris Pacheco, Nicole Phan, Falisha A. Porto, Edward T. Ryan, Kathleen Selleck, Sue Slaughenhaupt, Kimberly Smith Sheppard, Elizabeth Suschana, Vivine Wilson, Galit Alter, Alejandro B. Balazs, Julia Bals, Max Barbash, Yannic C. Bartsch, Julie Boucau, Josh Chevalier, Fatema Z. Chowdhury, Kevin Einkauf, Jon Fallon, Liz Fedirko, Kelsey Finn, Pilar García‐Broncano, Ciputra Adijaya Hartana, Chenyang Jiang, Paulina Kapłonek, Marshall Karpell, Evan C. Lam, Kristina Lefteri, Xiaodong Lian, Mathias Lichterfeld, Daniel Lingwood, Hang Liu, Jin-Qing Liu, Natasha Ly, Ashlin R. Michell, Ilan Millstrom, Noah Miranda, Claire O’Callaghan, Matthew R. Osborn, Shiv Pillai, Yelizaveta Rassadkina, Alexandra Reissis, Francis F. Ruzicka, Kyra Seiger, Libera Sessa, Christianne Sharr, Sally Shin, Nishant K. Singh, Weiwei Sun, Xiaoming Sun, Hannah Ticheli, Alicja Trocha-Piechocka, Daniel Worrall, Alex Zhu, George Q. Daley, David Golan, Howard M. Heller, Arlene Sharpe, Nikolaus Jilg, Alex Rosenthal, C. Jason Wong,

vaccines and immunoinformatics approaches

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.