β-Cell Dysfunction and Altered Thyroid Hormone Dynamics in Post-COVID Metabolic Disturbances: An Immunometabolic Cross-Sectional Study

Background: SARS-CoV-2 infection has been associated with metabolic disturbances and endocrine alterations, including effects on pancreatic β-cell function and thyroid hormone regulation. However, the relationship between thyroid function and β-cell compensatory capacity in the post-COVID state remains unclear. Methods: In this cross-sectional study, we evaluated β-cell compensation (HOMA-B/HOMA-IR) and thyroid parameters in three groups: patients with active COVID-19, individuals with post-COVID metabolic disturbances, and a COVID-negative metabolic syndrome reference group. Thyroid status was assessed using both comprehensive clinical classification and biochemical criteria. Associations between thyroid hormones and β-cell function were analyzed using Spearman correlation. Results: β-cell compensatory capacity differed significantly across groups, with the lowest values observed during active COVID-19 and intermediate impairment in the post-COVID cohort compared with the metabolic syndrome group. FT3 concentrations and the FT3/FT4 ratio were significantly reduced during active infection and were positively associated with β-cell compensation in the post-COVID group (ρ = 0.421, p = 0.018 and ρ = 0.382, p = 0.031, respectively). Although thyroid dysfunction appeared more prevalent in the post-COVID cohort when defined by overall clinical classification, no significant differences were observed when thyroid status was evaluated based solely on biochemical criteria, excluding clinical history and euthyroid sick syndrome. Conclusions: Post-COVID metabolic disturbances are characterized by impaired β-cell compensatory capacity and alterations in peripheral thyroid hormone dynamics. The apparent increase in thyroid dysfunction is largely driven by pre-existing thyroid disease and non-thyroidal illness effects rather than intrinsic thyroid pathology. These findings are consistent with the hypothesis of a potential post-COVID immunometabolic phenotype involving both pancreatic and thyroid-related mechanisms.