Background and aim: Environmental pollution interacting with genetic factors and infections can lead to autoimmunity. Evidence suggests that SARS-CoV-2 can trigger autoimmune responses and that autoimmunity plays a role in post-COVID symptoms. The present study explored associations between serum immunoglobulin G (IgG) responses to SARS-CoV-2 and autoantibody reactivity.

Methods: Cross-sectional serum samples from adult individuals diagnosed with COVID-19 from 15 to 60 days prior to sampling in 2020 – early 2021 (N = 187) were acquired from biobanks. Samples were tested for IgG responses to SARS-CoV-2 recombinant spike and nucleocapsid proteins using a previously developed in-house multiplex magnetic bead suspension immunoassay on the Luminex platform. Total serum IgG levels were measured using another in-house Luminex immunoassay. IgG responses to 18 self-antigens were measured using the Human Autoimmune Antibody multiplexed Luminex immunoassay from EMD Millipore; a log-transformed sum of all autoantibody responses was used as a measure of total autoantibody reactivity. Commercially available ELISA IgG assays were used to identify individuals seropositive to four common chronic infections that have been linked with various autoimmune conditions: cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, and Toxoplasma gondii.

Results: Greater antibody responses to the spike protein and its receptor binding domain were associated with significantly increased autoantibody responses. A ten-fold increase in anti-spike IgG was associated with 1.20 (1.05; 1.38)-fold increase in autoantibody reactivity; after adjusting for total IgG and cytomegalovirus seropositivity this association was reduced to 1.16 (1.01; 1.32)-fold. Associations between chronic infections and autoantibody responses were positive but not significant.  

Conclusion: This study produced evidence of autoimmune effects of SARS-CoV-2 infections. Further research is needed to characterize temporal trajectories of COVID-related autoantibody responses and their interactions with environmental triggers of autoimmunity.