Abstract
While there have been extensive analyses characterizing cellular and humoral responses across the severity spectrum in COVID-19, outcome predictors within severe COVID-19 remain less comprehensively elucidated. Furthermore, properties of antibodies (Abs) directed against viral antigens beyond spike and their associations with disease outcomes remain poorly defined. We perform deep molecular profiling of Abs directed against a wide range of antigenic specificities in severe COVID-19 patients. The profiles included canonical (spike [S], receptor-binding domain [RBD], and nucleocapsid [N]) and non-canonical (orf3a, orf8, nsp3, nsp13, and membrane [M]) antigenic specificities. Notably, multivariate Ab profiles directed against canonical or non-canonical antigens are equally discriminative of survival in severe COVID-19. Intriguingly, pre-pandemic healthy controls have cross-reactive Abs directed against nsp13, a protein conserved across coronaviruses. Consistent with these findings, a model built on Ab profiles for endemic coronavirus antigens also predicts COVID-19 outcome. Our results suggest the importance of studying Abs targeting non-canonical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and endemic coronavirus antigens in COVID-19.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; antibody profiling; cross-reactivity; endemic coronaviruses; non-canonical antigens; nsp13; systems immunology.
【저자키워드】 COVID-19, nsp13, cross-reactivity, Endemic coronaviruses, CP: Immunology, CP: Microbiology, antibody profiling, non-canonical antigens, systems immunology., 【초록키워드】 immunology, SARS-CoV-2, Coronaviruses, coronavirus, Microbiology, severe COVID-19, antibody, severity, outcome, Antigen, nsp13, cross-reactivity, Protein, specificity, survival, Viral, Receptor-binding domain, Humoral response, ORF3a, ORF8, nucleocapsid, membrane, Nsp3, predictor, molecular, respiratory, disease, predict, antibody profiling, association, cellular, Endemic, cross-reactive, Viral antigen, acute respiratory syndrome, viral antigens, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, profile, healthy control, antigenic, domain, severe COVID-19 patients, profiles, Specificities, while, Cellular and humoral responses, defined, conserved, less, analysis, canonical, 【제목키워드】 outcome, Antigen, Endemic, conserved, coronavirus,