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Diverse functional autoantibodies in patients with COVID-19

2021; Nature Portfolio; Volume: 595; Issue: 7866 Linguagem: Inglês

10.1038/s41586-021-03631-y

1476-4687

Eric Y. Wang, Tianyang Mao, Jon Klein, Yile Dai, John D. Huck, Jillian R. Jaycox, Feimei Liu, Ting Zhou, Benjamin Israelow, Patrick Wong, Andreas Coppi, Carolina Lucas, Julio Silva, Ji Eun Oh, Eric Song, Emily S. Perotti, Neil S. Zheng, Suzanne Fischer, Melissa Campbell, John Fournier, Anne L. Wyllie, Chantal B. F. Vogels, Isabel M. Ott, Chaney C. Kalinich, Mary E. Petrone, Anne E. Watkins, Abeer Obaid, Adam J. Moore, Arnau Casanovas‐Massana, Alice Lu-Culligan, Allison Nelson, Ángela Núñez, Anjelica Martin, Bertie Geng, Camila D. Odio, Christina A. Harden, Codruta Todeasa, Cole Jensen, Daniel Kim, David McDonald, Denise Shepard, Edward Courchaine, Elizabeth B. White, Erin Silva, Eriko Kudo, Giuseppe DeIuliis, Harold Rahming, Hong‐Jai Park, Irene Matos, Jessica Nouws, Jordan Valdez, Joseph K. Lim, Kadi-Ann Rose, Kelly Anastasio, Kristina Brower, Laura Glick, Lokesh Sharma, Lorenzo R. Sewanan, Lynda Knaggs, Maksym Minasyan, Maria Batsu, Maxine Kuang, Maura Nakahata, Melissa Linehan, Michael H. Askenase, Michael Simonov, Mikhail Smolgovsky, Nicole Sonnert, Nida Naushad, Pavithra Vijayakumar, Rick Martinello, Rupak Datta, Ryan Handoko, Santos Bermejo, Sarah Prophet, Sean Bickerton, Sofia Velazquez, Tyler Rice, William Khoury-Hanold, Xiaohua Peng, Yexin Yang, Yiyun Cao, Yvette Strong, Charles S. Dela Cruz, Shelli Farhadian, Wade L. Schulz, Shuangge Ma, Nathan D. Grubaugh, Albert I. Ko, Akiko Iwasaki, Aaron M. Ring,

Long-Term Effects of COVID-19

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes. Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.