Promising data have come out recently that points to a possible link between prostate cancer and COVID-19, where androgen-deprivation therapies used in prostate cancer have been shown to instigate a protective role against COVID-19. This is due to the crosstalk between COVID-19 and prostate cancer at the level of genetic aberrations and molecular signatures that are common between the two diseases, including AR and TMPRSS2. It is still not clear, however, whether higher expression of ACE2/TMPRSS2 is related to high viral load in the tissues, at least within the lung, for COVID-19 patients. The first/major line of exposure/defense against pathogens like SARS-CoV-2 are mucosal epithelial barriers in the host (e.g. respiratory, intestinal). Unfortunately, strategies to limit infection of these barriers by SARS-CoV-2 are proving to be contentious because there are multiple routes and mechanisms of entry.