mRNA-based COVID-19 vaccination and risk of autoimmune diseases in the pediatric population

Vaccine-related autoimmune diseases have been hypothesized for decades, but epidemiological studies have consistently shown no associations with routine childhood vaccinations. The introduction of mRNA-based COVID-19 vaccines renewed attention to this question, given theoretical mechanisms such as molecular mimicry and immune overactivation. Using medical records from the TriNetX US collaborative network, this study evaluated whether COVID-19 vaccination is associated with increased risk of autoimmune disease in children and explored the role of SARS-CoV-2 infection.

We analyzed autoimmune disease incidence trends among children aged 0-21 years from 2016 to 2024. Using a retrospective matched cohort study design with data from April 2020- April 2025, we compared: (1) vaccinated versus unvaccinated children (n = 936,919 versus 942,604), (2) vaccinated versus unvaccinated children with prior SARS-CoV-2 infection (n = 44,512 per group), and (3) vaccinated children with versus without prior infection (n = 43,170 per group). Autoimmune diagnoses (all conditions) were assessed during a fixed 180-day period after cohort entry. Cox proportional hazards models estimated hazard ratios (HRs).

Trend analysis showed an increase in pediatric autoimmune disease incidence beginning in 2021. In comparative analyses, vaccinated children had a significantly lower overall hazard of autoimmune disease during the 180-day follow-up than unvaccinated children (HR=0.387; 95% CI: 0.365-0.410). Among children with prior SARS-CoV-2 infection, vaccination again had a protective association compared to unvaccinated (HR=0.690; 95% CI: 0.516-0.922). No significant difference was observed between vaccinated children with and without prior infection.

These findings suggest COVID-19 vaccination is associated with a lower hazard of autoimmune disease in children, including those with prior SARS-CoV-2 infection.