Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Allergy and Clinical Immunology, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Front Immunol. 2023 Jun 21;14:1216211. doi: 10.3389/fimmu.2023.1216211. eCollection 2023.
Recently emerged reports indicated that patients with coronavirus disease 2019 (COVID-19) might experience novo genitourinary symptoms after discharge. Nevertheless, the causal associations and underlying mechanisms remain largely unclear.
Genome-wide association study (GWAS) statistics for COVID-19 and 28 genitourinary symptoms with consistent definitions were collected from the COVID-19 Host Genetic Initiative, FinnGen, and UK Biobanks. Mendelian randomization (MR) analyses were applied to explore the causal effects of COVID-19 on genitourinary symptoms by selecting single-nucleotide polymorphisms as instrumental variables. Meta-analyses were conducted to evaluate the combined causal effect. Molecular pathways connecting COVID-19 and its associated disorders were evaluated by weighted gene co-expression network analysis (WGCNA) and enrichment analyses to extract insights into the potential mechanisms underlying the connection.
The MR and meta-analyses indicated that COVID-19 was causally associated with increased risk for calculus of the lower urinary tract (LUTC, OR: 1.2984 per doubling in odds of COVID-19, 95% CI: 1.0752-1.5680, = 0.007) and sexual dysfunction (SD, OR: 1.0931, 95% CI: 1.0292-1.1610, = 0.004). Intriguingly, COVID-19 might exert a slight causal protective effect on the progression of urinary tract infections (UTIs) and bladder cancer (BLCA). These results were robust to sensitivity analyses. Bioinformatic analyses indicated that the inflammatory-immune response module may mediate the links between COVID-19 and its associated disorders at the molecular level.
In response to post-COVID-19 symptoms, we recommend that COVID-19 patients should strengthen the prevention of LUTC and the monitoring of sexual function. Meanwhile, the positive effects of COVID-19 on UTIs and BLCA should attach equal importance.
最近有报道称，新冠肺炎（COVID-19）患者出院后可能会出现新的泌尿生殖系统症状。然而，因果关联和潜在机制在很大程度上仍不清楚。
从 COVID-19 宿主遗传计划、芬兰基因和英国生物银行收集了 COVID-19 和 28 种具有一致定义的泌尿生殖系统症状的全基因组关联研究（GWAS）统计数据。通过选择单核苷酸多态性作为工具变量，应用孟德尔随机化（MR）分析来探讨 COVID-19 对泌尿生殖系统症状的因果影响。进行荟萃分析以评估 COVID-19 与泌尿生殖系统症状之间的综合因果效应。通过加权基因共表达网络分析（WGCNA）和富集分析，评估连接 COVID-19 与其相关疾病的分子途径，以提取潜在机制的见解。
MR 和荟萃分析表明，COVID-19 与下尿路结石（LUTC）的风险增加（每增加一倍 COVID-19 的几率，OR：1.2984，95%CI：1.0752-1.5680， = 0.007）和性功能障碍（SD，OR：1.0931，95%CI：1.0292-1.1610， = 0.004）存在因果关系。有趣的是，COVID-19 可能对尿路感染（UTI）和膀胱癌（BLCA）的进展产生轻微的因果保护作用。这些结果在敏感性分析中是稳健的。生物信息学分析表明，炎症-免疫反应模块可能在分子水平上介导 COVID-19 与其相关疾病之间的联系。
针对 COVID-19 后症状，我们建议 COVID-19 患者应加强对 LUTC 的预防和性功能监测。同时，应同等重视 COVID-19 对 UTI 和 BLCA 的积极影响。
