Autoantibody seroprevalence in clinical laboratory testing pre- and post-COVID-19

Objectives Viral infections are recognized contributors to the development or induction of autoimmune diseases, and COVID-19 has been associated with transient autoantibody formation and increased risk of new-onset autoimmune conditions. While individual-level risk is established, it is unclear whether these effects translate into measurable changes in positivity rates for autoimmune serology tests within the clinical laboratory. Methods We retrospectively compared the proportion of positive autoimmune serology tests performed in a large academic clinical laboratory during 2019 (pre-pandemic) and 2022 (post-pandemic). Assays included: antinuclear antibody (ANA) indirect immunofluorescence, extractable nuclear antigens (ENA), antineutrophil cytoplasmic antibodies (ANCA), and organ-specific autoantibodies. Results ANA reactivity was stable between 2019 (39.0 %) and 2022 (39.2 %, p=0.84). ANA titers had a greater proportion of high-titer results in 2022 (≥1:2,560: 0.1 vs. 6.6 %, p<0.0001). Homogeneous patterns increased (42.8% vs. 47.6 %, p=0.0047), while cytoplasmic patterns decreased (21.5% vs. 13.3 %, p<0.0001). ANCA positivity declined (15.6% vs. 9.5 %, p<0.0001). For organ-specific markers, anti-TPO positivity decreased (46.9% vs. 39.8 %, p<0.0001), although titers were higher in 2022 (p<0.0001). Other markers showed mixed or nonsignificant trends. Conclusions Although COVID-19 increases individual risk for autoimmune disease, we found no rise in overall autoantibody positivity at the clinical laboratory level. Positivity rates were stable or decreased, with some titers higher among positive cases. These findings suggest individual risk does not translate into detectable shifts at the laboratory level, underscoring the need for broader, longitudinal studies to define the long-term impact of COVID-19 and other viral outbreaks on the burden of autoimmune diseases.