Distinct circulating autoantibodies are associated with COVID-19 hospitalization and SARS-CoV-2 neutralization activity

SARS-CoV-2 infection disrupts the host’s immune system, altering autoimmune responses. This study investigated host autoreactivities in SARS-CoV-2 infections, their association with severe COVID-19, and the neutralizing antibody response. Circulating autoantibodies were detected in convalescent serum samples from unvaccinated SARS-CoV-2-infected patients. Clustering, correlation analysis, principal component analysis, and neural network modeling were used to explore the relationship between autoantibodies, hospitalization, and SARS-CoV-2 neutralization. The presence of one autoantibody correlated with the detection of multiple others. Anti-IFNα antibodies were associated with elevated levels of anti-ENAs (extractable-nuclear antigen) but not with clinical outcome. COVID-19 hospitalization was significantly associated with the collective expression of autoantibodies targeting three ENAs: SSA/Ro52, Jo-1, and RNP. In contrast, autoantibodies targeting RNP/Sm, PCNA, Scl-70, and PL-12 were strongly associated with SARS-CoV-2 neutralization. In summary, this study has identified self-antigens targeted in hospitalized COVID-19 patients and highlights a novel association between the autoantibody response and the antiviral humoral response.