Autoimmune Manifestations Following COVID-19 Infection: A Systematic Review

Coronavirus disease 2019 (COVID-19) has been linked to immune dysregulation and autoantibody formation, raising concern that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may precipitate new-onset autoimmune disease. This systematic review synthesises controlled observational evidence on the incidence and risk of autoimmune manifestations following confirmed COVID-19. Following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines, electronic databases were searched from inception upto the search date for original cohort or case-control studies comparing incident autoimmune disease in individuals with versus without confirmed COVID-19. Eligibility was structured using the PICOS (Population, Intervention/Exposure, Comparator, Outcome, and Study design) framework. Methodological quality was appraised using the Newcastle-Ottawa Scale and certainty of evidence using the GRADE approach. Findings were synthesised narratively. Eight large cohort studies, drawn from multiple national health systems and collectively encompassing tens of millions of individuals, met the inclusion criteria. Confirmed SARS-CoV-2 infection was consistently associated with an increased risk of incident autoimmune disease spanning rheumatological, dermatological, vasculitic, endocrine, gastrointestinal, haematological, and neurological domains, with adjusted hazard ratios ranging from approximately 1.3 to 3.0. Connective tissue, vasculitic, and antibody-mediated disorders were most frequently implicated. Several studies demonstrated a severity-dependent gradient and attenuation of risk over time, and one cohort reported a reduced risk among vaccinated individuals. The overall certainty of evidence was low to moderate. Confirmed COVID-19 is associated with an increased, though in absolute terms modest, risk of new-onset autoimmune disease, most reproducibly affecting connective tissue, vasculitic, and antibody-mediated conditions. The observational evidence supports clinical vigilance, particularly after severe infection, while prospective studies with validated outcomes and infection comparators are needed to confirm causality.