Covid-19 in Man: A Very Dangerous Affair

The novel pandemic of Coronavirus disease 2019 (COVID-19) has become a public health issue since March 2020, with more than 30 million people found to be infected worldwide. Men may be considered to be at a higher risk of poor prognosis or death once the infection occurred. Concerns surfaced regarding the risk of a possible testicular injury due to SARS-CoV-2 infection. Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On the one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS₂) and angiotensin-converting enzyme 2 (ACE₂). At the same time, a younger man with normal testicular function compared to a woman of similar age is prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that the SARS-CoV-2 genome is not normally found in gonads and gametes. Therefore, transmission through sex could be excluded as a possible way to spread the COVID-19. Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection, even if it occurred asymptomatically. Still, no long-term evidence is currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.