LAUSR

Coronavirus disease 2019 (COVID‐19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre‐existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID‐19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self‐antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID‐19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus‐2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti‐type I IFN autoantibodies or neutralizing anti‐type I IFN activity of plasma samples from the two patient groups. Increased anti‐type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)‐229E and HCOV‐NL63 spike proteins were associated with mild disease outcome. COVID‐19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long‐term humoral immunity against HCOV‐22E and HCOV‐NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life‐threatening COVID‐19 is critical to reducing mortality and morbidity.