Long-term risk of incident autoimmune thyroid disease after COVID-19 in patients with type 2 diabetes: a multicenter propensity score-matched cohort study.

Background: Viral infections have been implicated in thyroid autoimmunity, and COVID-19 has emerged as a possible trigger. However, current evidence is mostly limited to case reports and short-term studies evaluating broad thyroid dysfunction rather than autoimmune-specific thyroid disease. This study aimed to evaluate whether documented SARS-CoV-2 infection is associated with a delayed and increased long-term risk of incident autoimmune thyroid disease in adults with type 2 diabetes. Methods: We used the TriNetX Global Collaborative Network to conduct a retrospective multicenter cohort study of adults with type 2 diabetes who had documented COVID-19 between January 2020 and June 2022 and matched controls without a documented SARS-CoV-2 infection. Patients with a history of thyroid disease were excluded. After 1:1 propensity score matching, a 12-month landmark design was applied. Follow-up was extended from day 365 to day 2190 after cohort entry. Incident Hashimoto's thyroiditis and Graves' disease were defined as primary outcomes, whereas hypothyroidism and all-cause mortality were assessed as secondary outcomes. Results: After matching, 590,346 patients were included in each cohort, with a mean age of 61.8 years. During follow-up, COVID-19 was associated with higher risks of incident Hashimoto's thyroiditis (649 vs. 511 events; HR, 1.56; 95% CI, 1.39-1.75) and Graves' disease (467 vs. 299 events; HR, 1.92; 95% CI, 1.66-2.23; both p<0.001). Increased risks were also observed for hypothyroidism (HR, 1.61; 95% CI, 1.57-1.65) and all-cause mortality (HR, 1.68; 95% CI, 1.65-1.71). The associations persisted across the sensitivity analyses and were consistent across sex and age subgroups. Landmark analyses using 3- and 24-month event-free intervals showed stronger associations over time for outcomes. In an exploratory analysis restricted to patients with COVID-19, pre-index vaccination was associated with a lower risk of Hashimoto's thyroiditis but not with Graves' disease, hypothyroidism, or all-cause mortality. Conclusions: Among adults with type 2 diabetes, documented COVID-19 was associated with an increased risk of delayed-onset autoimmune thyroid disease beyond the first post-infection year. Given the observational design and low absolute event rates, these findings do not establish causality but support targeted clinical vigilance and prospective validation using antibody-confirmed outcomes.