Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection: Bioinformatics and molecular simulation analyses

Kai Zhao; Dong Zhang; Xinchi Xu; Shangqian Wang; Zhanpeng Liu; Xiaohan Ren; Xu Zhang; Zhongwen Lu; Shancheng Ren; Chao Qin

doi:10.1016/j.ajur.2022.12.004

Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection: Bioinformatics and molecular simulation analyses

Asian J Urol. 2023 Feb 7;10(3):344-355. doi: 10.1016/j.ajur.2022.12.004. Online ahead of print.

Authors

Kai Zhao^{1

2}, Dong Zhang^{1

2}, Xinchi Xu^{1

2}, Shangqian Wang^{1

2}, Zhanpeng Liu^{1

2}, Xiaohan Ren^{1

2}, Xu Zhang^{1

2}, Zhongwen Lu^{1

2}, Shancheng Ren³, Chao Qin^{1

2}

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
² The State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
³ Department of Urology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China.

Abstract

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.

Keywords: ACE2; CD147; Coronavirus disease 2019; Genitourinary organ; Severe acute respiratory syndrome coronavirus 2; TMPRSS2; Testosterone.