Association Between COVID-19 Infection and Thyroid Cancer Development: A Retrospective Cohort Study Using the TriNetX Database

<b>Background</b>: Coronavirus Disease 2019 has been associated with dysfunction in multiple endocrine organs, including the thyroid gland. While evidence suggests SARS-CoV-2 may influence thyroid function and promote oncogenesis through inflammation and cytokine storms, its role in thyroid cancer remains unclear. This study investigates whether COVID-19 is associated with an increased risk of thyroid cancer development. <b>Methods</b>: We conducted a retrospective cohort study using the TriNetX global federated health research database, encompassing data from 151 healthcare organizations. Adult patients with confirmed COVID-19 between 1 December 2019 and 31 December 2023, were included and compared to a matched cohort without COVID-19. Patients with prior thyroid cancer history or who had received COVID-19 vaccination were excluded in both groups. Propensity score matching (1:1) was performed for age, gender, and overweight/obesity status. The primary outcome was that new-onset thyroid cancer was diagnosed at least one year after COVID-19 diagnosis. Hazard ratios were calculated using Cox proportional hazards models, and subgroup analyses were performed based on age, gender, thyroid function status and treatment modalities. <b>Results</b>: After matching, a significantly higher thyroid cancer incidence was observed between the post-COVID and non-COVID groups. Subgroup analysis revealed a significantly higher risk of thyroid cancer development following COVID-19 diagnosis in patients who developed hyperthyroidism (HR 2.14, 95% CI: 1.04-4.46) or hypothyroid-ism (HR 1.83, 95% CI: 1.12-2.97) compared with the non-COVID population. Male patients also exhibited a higher risk of thyroid cancer after COVID-19 (HR 1.22, 95% CI 1.02-1.46). For patients with hyperthyroidism or hypothyroidism, those who had prior COVID-19 exhibited a relatively higher risk of developing thyroid cancer than those without a history of COVID-19 (HR 4.387, 95% CI: 2.08-9.24 for hyperthyroidism; HR 2.58, 95% CI: 1.58-4.22 for hypothyroidism). <b>Conclusions</b>: Patients with COVID-19 exhibited an increase in thyroid cancer risk, with specific subgroups-male adults and those with post-infectious thyroid dysfunction-also exhibiting increased risk. These findings suggest a potential relationship between SARS-CoV-2 and thyroid oncogenesis, warranting further prospective research.