Department of Thyroid Breast Surgery, Xi'an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, 710018, P.R. China.
Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
Endocrinology. 2022 Oct 11;163(11). doi: 10.1210/endocr/bqac139.
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 largest publicly available 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 susceptibility (cases = 38 984; controls = 1 644 784), hospitalization (cases: 9986 = controls = 1 877 672), and very severe disease (cases = 5101; controls = 1 383 241) of COVID-19 were used as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis, and utilized MR-Egger regression, weighted median, and robust adjusted profile score (RAPS) for sensitivity analysis. Genetic predisposition to higher serum levels of FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (odds ratio [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.
几项观察性研究证实了甲状腺激素与 2019 年冠状病毒病（COVID-19）之间的关系，但这种相关性仍存在争议。我们基于最大的公开汇总数据集进行了两样本孟德尔随机化（MR）分析。使用 49269 名个体的游离甲状腺素（FT4）和 54288 名个体的促甲状腺激素（TSH）汇总统计数据作为暴露工具。COVID-19 易感性（病例=38984；对照=1644784）、住院（病例：9986=对照=1877672）和非常严重疾病（病例=5101；对照=1383241）的全基因组关联研究被用作结果。我们使用逆方差加权（IVW）方法作为主要分析方法，并利用 MR-Egger 回归、加权中位数和稳健调整的轮廓得分（RAPS）进行敏感性分析。正常范围内血清 FT4 水平升高的遗传易感性与 COVID-19 住院（优势比[OR] = 0.818；95%置信区间，0.718-0.932；P = 2.6×10-3）和非常严重疾病（OR = 0.758；95%置信区间，0.626-0.923；P = 5.8×10-3）的风险呈负相关，但与易感性无关。没有证据表明遗传预测的循环 TSH 水平与 COVID-19 的易感性和严重程度风险相关。敏感性分析中未发现明显的异质性或混杂性。总之，我们发现较高的 FT4 水平可能降低 COVID-19 严重程度的风险，这表明 COVID-19 患者可能需要进行甲状腺功能检测。
