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Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms

2021; Elsevier BV; Volume: 2; Issue: 5 Linguagem: Inglês

10.1016/j.xcrm.2021.100288

2666-3791

Eric Song, Christopher M. Bartley, Ryan D. Chow, Thomas Ngo, Ruoyi Jiang, Colin R. Zamecnik, Ravi Dandekar, Rita P. Loudermilk, Yile Dai, Feimei Liu, Sara Sunshine, Jamin Liu, Wesley Wu, Isobel A. Hawes, Bonny D. Alvarenga, Trung Huynh, Lindsay McAlpine, Nur-Taz Rahman, Bertie Geng, Jennifer Chiarella, Benjamin Israelow, Chantal B. F. Vogels, Nathan D. Grubaugh, Arnau Casanovas‐Massana, Brett S. Phinney, Michelle Salemi, Jessa Alexander, Juan A. Gallego, Todd Lencz, Hannah Walsh, Anne E. Wapniarski, Subhasis Mohanty, Carolina Lucas, Jon Klein, Tianyang Mao, Ji-Eun Oh, Aaron M. Ring, Serena Spudich, Albert I. Ko, Steven H. Kleinstein, John E. Pak, Joseph L. DeRisi, Akiko Iwasaki, Samuel J. Pleasure, Michael R. Wilson, Shelli Farhadian,

COVID-19 Clinical Research Studies

Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19.