Vaccination prior to SARS-CoV-2 infection reduces autoreactive antibody induction

Abstract SARS-CoV-2 infection leads to diverse outcomes ranging from asymptomatic infection to death. Several studies reported elevated autoreactive antibodies in SARS-CoV-2-infected individuals compared to healthy controls, suggesting SARS-CoV-2 infection promotes autoantibodies, which could increase the risk of autoimmunity. However, it is not known whether autoreactive antibodies observed after infection were present in individuals prior to infection. Further, the prevalence, duration, and vaccine impact on autoreactive antibodies are unresolved. Since elevated autoreactive antibodies precede the onset of autoimmune disease, it is important to investigate the impact of SARS-CoV-2 infection on self-reactive antibodies. We established a longitudinal study to collect baseline PBMC and plasma samples from participants at enrollment, beforeSARS-CoV-2 infection or vaccination. Participants were screened weekly by nasal swab PCR to detect asymptomatic infection. Additional samples were collected after confirmed SARS-CoV-2 infection and assessed for autoreactive antibodies predictive of various autoimmune disorders. Preliminary analysis showed that a subset of individuals exhibited an increase in autoreactive antibodies following infection, while other individuals unexpectedly displayed decreased levels. Notably, individuals infected after vaccination displayed fewer changes in autoreactive antibodies compared to infection prior to vaccination. Our data suggest that SARS-CoV-2 infection increases specific autoreactive antibody levels but does not induce a widespread increase in all autoreactive antibodies. Moreover, SARS-CoV-2 vaccination prior to infection reduced autoantibody induction. Supported by grants from NIH CEIRS HHSN272201400006C and Household Respiratory Virus SARS-CoV-2 Transmission and Immunity Sub-Study (HRTS) 3U01AI144616-02S1