Recent SARS-CoV-2 infections and increased antibody responses to viral antigens are associated with greater autoantibody reactivity.
BACKGROUND SARS-CoV-2-induced latent autoimmunity may play a role in long-COVID symptoms. This study explored associations between serum immunoglobulin G (IgG) responses to 18 self-antigens and antibody responses to SARS-CoV-2 and common chronic infections: Epstein-Barr virus (EBV), cytomegalovirus (CMV), Helicobacter pylori, and Toxoplasma gondii. METHODS This cross-sectional study used 179 SARS-CoV-2 convalescent serum samples acquired from biobanks and 123 pre-pandemic serum samples. IgG responses to SARS-CoV-2 spike, receptor binding domain, spike subunit 2, and nucleocapsid antigens were measured using an in-house Luminex multiplexed suspension fluorescence immunoassay. IgG responses to four chronic infections were quantified using commercial ELISA kits. Autoantibody responses to 18 self-antigens were simultaneously measured using a commercially available multiplexed Luminex assay; combined autoantibody reactivity was defined as the geometric mean of the 18 individual autoantibody responses. RESULTS Combined autoantibody reactivity and responses to several individual self-antigens were significantly higher in SARS-CoV-2 convalescent, seropositive individuals than in seronegative pre-pandemic controls. Associations between CMV, EBV, H. pylori, and T. gondii seropositivity and combined autoantibody reactivity were not statistically significant. Stronger antibody responses to antigens of the SARS-CoV-2 spike protein (S, S2, and RBD) in convalescent individuals were significantly associated with greater combined autoantibody reactivity and increased responses to multiple individual self-antigens. Conversely, antibody responses to antigens of CMV, EBV, H. pylori, and T. gondii in corresponding subsets of seropositive individuals were not associated with combined autoantibody reactivity. CONCLUSION SARS-CoV-2 infection and the intensity of IgG responses to the spike protein were associated with increased autoantibody reactivity, a potential indicator of latent autoimmunity.