P. Lamy, X. Rébillard, F. Vacherot, A. de la taille
World Journal of Urology, 2020
According different studies and reports by live gender data tracker, more infected men than women seem to be dying from the new coronavirus, in different countries hit by the pandemic [1, 2]. In France, during March 2020 we observed a more pronounced excess mortality in men than in women (+ 13%) compare to March 2019 and 2018. The excess mortality was even higher in region registering high rate of COVID-19 in North and East France [3]. Men can be more susceptible to viruses than women. Women generally tend to have stronger immune responses to viruses, though the reason for that is still up for debate. Genetic and hormonal differences may play a role, while environmental factors could also contribute to susceptibility to different viruses. During previous epidemics of coronaviruses, male sex was associated with worse clinical outcomes due to severe acute respiratory syndrome (SARS) in Hong Kong [4], and a higher risk of dying from Middle East respiratory syndrome (MERS) [5]. As specialists of prostate cancer, we were particularly interested to learn SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. SARS-CoV-2 may even require the combined presence of ACE-2 and TMPRSS2 to enter cells [6]. TMPRSS2 is a transmembrane serine protease. Its expression is regulated by the androgen receptor and is abundantly expressed in the prostate. TMPRSS2 is overexpressed in advanced and metastatic prostate cancers. It has been shown that blockage of AR activity by androgen deprivation therapy reduces significantly the TMPRSS2 transcripts [7]. Considering this interplay, we hypothesize that androgens could upregulate TMPRSS2 expression in pneumocytes and consequently facilitates the viral entry into target cells. Augmented TMPRSS2 expression was also found to be associated with increased risk of severe influenza upon infection with the 2009 H1N1 pandemic virus and with increased susceptibility to H7N9 FLUAV infection [8]. TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV2 infection as it was demonstrated with SARS-CoV [9]. It could be also related with severity and mortality of the disease. TMPRSS2 knockout mice have less viral replication in the lungs than wild-type mice, and less severe immunopathology, resulting in milder lung pathology [10]. Patients with lung cancer showed also higher susceptibility to SARSCoV2 possibly related with high expression of TMPRSS2 in normal lung tissue [11]. A putative androgen dependence for virus cell entry relative to high expression of TMPRSS2 in men could explain the male mortality displacement. To our knowledge, there is few comparisons between men and women on TMPRSS2 respiratory tract expression. Recently, in a study comparing patients with severe asthma and healthy people, gene expression of ACE2 and TMPRRS2 were similar in the both groups. However, among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was associated with higher expression of ACE2 and TMPRSS2 [12]. All those correlations are consistent with Covid-19 risk factors previously described. In another study, TMPRRS2 is slightly increased in the lung in men [13]. The authors * Pierre-Jean Lamy Pierre-Jean.Lamy@labosud.fr
Cited by 6 publications.
Field of study: Medicine