학술논문
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms.
Document Type
article
Author
Song, Eric; Bartley, Christopher M; Chow, Ryan D; Ngo, Thomas T; Jiang, Ruoyi; Zamecnik, Colin R; Dandekar, Ravi; Loudermilk, Rita P; Dai, Yile; Liu, Feimei; Sunshine, Sara; Liu, Jamin; Wu, Wesley; Hawes, Isobel A; Alvarenga, Bonny D; Huynh, Trung; McAlpine, Lindsay; Rahman, Nur-Taz; Geng, Bertie; Chiarella, Jennifer; Goldman-Israelow, Benjamin; Vogels, Chantal BF; Grubaugh, Nathan D; Casanovas-Massana, Arnau; Phinney, Brett S; Salemi, Michelle; Alexander, Jessa R; Gallego, Juan A; Lencz, Todd; Walsh, Hannah; Wapniarski, Anne E; Mohanty, Subhasis; Lucas, Carolina; Klein, Jon; Mao, Tianyang; Oh, Jieun; Ring, Aaron; Spudich, Serena; Ko, Albert I; Kleinstein, Steven H; Pak, John; DeRisi, Joseph L; Iwasaki, Akiko; Pleasure, Samuel J; Wilson, Michael R; Farhadian, Shelli F
Source
Cell reports. Medicine. 2(5)
Subject
Language
Abstract
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.