4.7 Urogenital injury in COVID-19
The NATURE has showed that the testosterone to luteinizing hormone (T to LH) ratio in 81 patients with COVID-19 was decreased in comparison with 100 age-matched healthy counterparts(Wang et al. , 2020). Serum T to LH ratio could be a potential marker of impairment of reproductive health by SARS-CoV-2. They considered that high levels of cytokines following viral or bacterial infection, illness or injury can cause deterioration in spermatogenesis and steroidogenesis, adversely affecting fertility. In the same time, the other study has demonstrated that females were able to achieve viral clearance significantly earlier than males, while they also have found that the ACE2 expression in testes, accompany with the lungs and kidneys, was highest consulting in three independent databases(Shastri et al. , 2020). Using online datasets, Fan and colleagues clearly demonstrated that ACE2 is highly expressed in Leydig cells and cells of the seminiferous tubules in the human testis(Fan et al. , 2020). Interestingly, very little expression of ACE2 was found in ovarian tissue. Instead of the SARS-CoV-2, viruses such as HIV, hepatitis B and C, mumps and papilloma have been proved that they can cause viral orchitis and even lead to male infertility and testicular tumors(Feichtinger et al. , 1992; Poretsky et al. , 1995; Tessler et al. , 1987). Meanwhile, the testis autopsy specimens obtained from six patients who died of SARS-CoV showed that the virus could induce orchitis(Xu et al. , 2006). Surprisingly, SARS-CoV-2 particles could be found in the epithelial cells of testicular seminiferous tubules and Leydig cells, providing direct evidence of viral testicular damage(Fan et al. , 2020). Evidences have identified that ACE2 was highly expressed in human testis(Donoghue et al. , 2000; Harmer et al. , 2002; Tipniset al. , 2000), which suggested the testis has the potential possiblity to be infected by the SARS-CoV-2 virus. The combination of SARS-CoV-2 with these ACE2-positive cells provided a site for infection and caused severe alteration of testicular tissue. Therefore, the urogenital organs should be a significant concern when evaluating the prognosis of COVID-19.
5. Therapeutic strategy of COVID-19 by rebalancing the RAAS axes
There are several potential approaches to address ACE2-mediated COVID-19. On the one hand, selectively blocking the combination of S protein and ACE2 may be an effective route; On the other hand, rebalancing the RAAS axes may improve inflammation.