Background. The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue
since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent
evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and
concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection.
Results. Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with
COVID-19. On 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, younger man with normal testicular function compared to women of similar age are 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 SARS-CoV-2
genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to
spread the COVID-19.
Conclusion. 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 in case it occurred asymptomatically but no long-term evidences are 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.