LAUSR

Several observational studies have confirmed the relationship between thyroid hormones and Coronavirus disease 2019 (COVID-19), but this correlation remains controversial. We performed a two-sample Mendelian Randomization (MR) analysis based on the public available largest summary datasets. Summary statistics with 49,269 individuals for free thyroxine (FT4) and 54,288 for thyroid stimulating hormone (TSH) were used as exposure instruments. Genome-wide association studies of the susceptibility (N = 1,644,784), hospitalization (N = 1,887,672) and very severe disease (N = 1,383,241) of COVID-19 were used as the outcome. We used the inverse variance weighted (IVW) method as the primary analysis, and MR-Egger regression, weighted median, and Robust Adjusted Profile Score (RAPS) were utilized as sensitivity analysis. Genetic predisposition to higher serum levels FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (OR = 0.818; 95%CI = 0.718-0.932; P = 2.6 × 10-3) and very severe disease (OR = 0.758; 95%CI = 0.626-0.923; P = 5.8 × 10-3), but not susceptibility. There is no evidence that genetically predicted circulating TSH levels are associated with COVID-19 susceptibility and severity risk. Neither apparent pleiotropy nor heterogeneity were detected in the sensitivity analysis. In summary, we found that higher FT4 levels may reduce the risk of COVID-19 severity, suggesting that thyroid function testing may be required for patients with COVID-19.