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Published on: December 1, 2017
The genetic associations of COVID-19 on genitourinary symptoms
Zhenglin Chang1,2,3, Lingyue An4, Min Lei5,6
1Department 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.
Insights
COVID-19 increases the risk of lower urinary tract calculus and sexual dysfunction. However, it may offer a protective effect against urinary tract infections and bladder cancer, with inflammation potentially mediating these effects.
Area of Science:
- Genetics and Epidemiology
- Infectious Diseases
- Urology
- Immunology
Background:
- Emerging reports suggest post-discharge genitourinary symptoms in COVID-19 patients.
- Causal links and mechanisms for these symptoms remain largely unknown.
- Understanding these associations is crucial for patient management.
Purpose of the Study:
- To investigate the causal relationship between COVID-19 and genitourinary symptoms.
- To explore potential molecular mechanisms underlying these associations.
- To provide evidence-based recommendations for post-COVID-19 care.
Main Methods:
- Utilized Genome-Wide Association Study (GWAS) statistics for COVID-19 and 28 genitourinary symptoms.
- Applied Mendelian Randomization (MR) analyses with single-nucleotide polymorphisms as instrumental variables.
- Conducted meta-analyses, Weighted Gene Co-expression Network Analysis (WGCNA), and enrichment analyses.
Main Results:
- COVID-19 causally associated with increased risk of lower urinary tract calculus (LUTC) and sexual dysfunction (SD).
- COVID-19 showed a potential protective effect on urinary tract infections (UTIs) and bladder cancer (BLCA).
- Inflammatory-immune response pathways identified as potential mediators.
Conclusions:
- Recommend enhanced prevention of LUTC and monitoring of SD in COVID-19 patients.
- Highlight the need to acknowledge potential positive effects on UTIs and BLCA.
- Suggest that inflammatory-immune responses may link COVID-19 to genitourinary conditions.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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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