Gender and sex hormones
Circulating plasma levels of ACE2 have been demonstrated to be higher in men with heart failure than in women and might indicate higher tissue expression of the SARS-CoV-2 entry receptor in man as a risk factor for more fatal courses of COVID-19 (27 ). The expression of ACE2 in the myocard is regulated by androgen in mouse models (28, 29 ). Male mice with hypertension had higher ACE2 expression, which was reduced after orchiectomy. These data indicate that testosterone might negatively impact on the risk for COVID-19.
In a study on patients with asthma, male gender, African Americans race and history of diabetes mellitus, was associated with higher expression of ACE2 and TMPRSS2 in sputum cells of patients with asthma (30 ).
Whether gender differences in terms of nature and frequency of the skin lesions exist, needs to be elucidated in further studies.
However, several gender differences in relation to virus responses and responses to viral vaccines have been described in the past. These include higher susceptibility of men to infectious diseases or stronger antibody titers inducible by a number of different types of vaccines in women as opposed to men. Moreover, plasmacytoid dendritic cell-mediated type I IFN responses have been demonstrated to be stronger in women than in men, another factor of putative importance for viral clearance even in the context of SARS-CoV-2 infections (31, 32 ). Higher susceptibility, need for hospitalization, longer duration of the disease and higher rate of mortality in men versus women has been also described for other virus infections such as with influenza virus (33 ). Together, these observations point to SARS-CoV-2 specific as well as general differences in viral immunity in man versus women.