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Published on: December 1, 2017
Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019
Kai Zhao1,2, Dong Zhang1,2, Xinchi Xu1,2
1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Objective:
The novel coronavirus (severe acute respiratory syndrome coronavirus 2) has been spreading worldwide since December 2019, posing a serious danger to human health and socioeconomic development. A large number of clinical trials have revealed that coronavirus disease 2019 (COVID-19) results in multi-organ damage including the urogenital system. This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.
Methods:
We used multiple publicly available databases to explore the expression patterns of ACE2, TMPRSS2, and CD147 (Basigin [BSG]) in major organs in the healthy and disease-specific populations, particularly the genitourinary organs. Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2, TMPRSS2, CD147, cytokine receptors, and cytokine interacting proteins in genitourinary organs, such as the bladder, kidney, prostate, and testis. Additionally, gene set enrichment analysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.
Results:
The results revealed that ACE2, TMPRSS2, and CD147 were highly expressed in normal urogenital organs. Then, they were also highly expressed in multiple tumors and chronic kidney diseases. Additionally, ACE2, TMPRSS2, and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing. Cytokine receptors and cytokine interacting proteins, especially CCL2, JUN, and TIMP1, were commonly highly expressed in urogenital organs. Finally, gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK/STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.
Conclusion:
Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives, which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can damage the genitourinary system. This study reveals SARS-CoV-2 entry proteins are highly expressed in urogenital organs, suggesting potential mechanisms for COVID-19-related genitourinary damage.
Area of Science:
- Urology
- Virology
- Bioinformatics
- Molecular Biology
Background:
- The novel coronavirus (SARS-CoV-2) causes COVID-19, leading to multi-organ damage.
- Genitourinary system damage has been observed in COVID-19 patients.
- Understanding the molecular mechanisms of genitourinary involvement is crucial.
Purpose of the Study:
- To investigate the potential mechanisms of genitourinary damage caused by SARS-CoV-2.
- To analyze the expression of key SARS-CoV-2 entry proteins in the genitourinary system.
- To explore the link between COVID-19 and genitourinary conditions using bioinformatics.
Main Methods:
- Utilized public databases to examine ACE2, TMPRSS2, and CD147 expression in genitourinary organs.
- Employed single-cell RNA sequencing to determine cell-specific expression patterns.
- Conducted gene set enrichment analysis to assess relationships with testosterone levels and signaling pathways.
Main Results:
- ACE2, TMPRSS2, and CD147 were highly expressed in healthy and diseased urogenital organs, including tumors and chronic kidney disease.
- Single-cell analysis confirmed significant expression of these proteins and related cytokine signaling molecules in genitourinary cells.
- High testosterone levels in prostate cancer patients correlated with COVID-19-associated JAK/STAT and Toll-like receptor pathways.
Conclusions:
- This study elucidates potential molecular mechanisms underlying SARS-CoV-2-induced genitourinary damage.
- Findings highlight the expression of viral entry proteins in the urogenital tract.
- Results may guide the development of targeted therapies for COVID-19-related genitourinary complications.
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