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.