Coronavirus disease 2019 (COVID-19) death rate differs depending on sex: in Chinese confirmed cases, while the infection rate among men and women is similar, the death rate among men is 4.7% compared with 2.8% for women 1. Italian data are similar as the reported death rate in men is significantly higher than that in women, 16.6% vs. 9.1%, respectively. Moreover, preliminary data from Italian epidemics suggest also a significant sex difference in infection rate, being 52.5% in women and 47.5% in men (Integrated Surveillance on COVID19 epidemic in Italy published by Italian Institute of Health, April 28th 2020, https://www. epicentro. iss. it/coronavirus/bollettino/Bollettino-sorveglianza-integrata-COVID-19_28-aprile_2020. pdf).

So far, the mechanisms underlying the observed gender bias are not disclosed; however, some hypotheses can be put forward on the basis of current knowledge on gender differences in respiratory viral diseases. The sex different lifestyles, such as smoking addiction that is prevalent in men than in women, is considered one of the potential risk factor for developing pneumonia consequent to COVID-19 2. In addition, it is known that, in general, innate and immune responses are more intense and stronger in females than in males 3. This can provide women with a more effective weapon to fight new and infective pathogens, favouring viral clearance. However, further factors could be taken into account in order to explain the sex bias in COVID-19 death rates. In particular, the human angiotensin-converting enzyme 2 (ACE2), an essential enzyme of the renin–angiotensin system (RAS), is the functional receptor for the severe acute respiratory syndrome coronavirus (SARS-CoV) as well as for the recently identified SARS-CoV-2 4, 5. It has been shown that ACE2 plays a protective role in chronic