Publication date: May 03, 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, p = 0. 007) and sexual dysfunction (SD, OR: 1. 0931, 95% CI: 1. 0292-1. 1610, p = 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.

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