COVID-19 and sex differences: is the men at risk?

Dear Colleagues，

Study about gender distribution, suggested that males account for 60% of COVID-19 patients. Reasons are not well explored yet. Some studies showed that even MERS-CoV and SARS-CoV infected more males than females. Pre-existing diseases, such as cardiovascular or respiratory impairment, hypertension or diabetes may unfavorably impact the course of the COVID-19. However, higher risk behaviors, such as alcohol abuse and smoking, more common in male than female, may play a role in the pathophysiological process of COVID-19. However, it has been reported that hormones such as sex-specific steroids (estrogens, androgens and progesterone), and activity of X-linked genes, exert different effects on immune regulation. In fact, these modulate the innate and adaptive immune response to virus infection and influence the immune response. It is well known that estrogen suppresses T and B cell lymphopoiesis, activates B cell function and influences T cell development. Moreover, estrogen regulates a number of cytokines (such as IL-1, IL10, and IFN-beta) that modulate the immune response. Progesterone increased IL-4, reduced IFN-beta (Th17) responses and reduced T cell proliferation and T cell dependent antibody responses. However, in CD8 T cells, progesterone reduced IFN-beta and cytotoxicity. Other possible explanation about these differences between male and female subjects could be related to a higher number and activity of innate immune cells in women. In particular, females are mosaics for X-linked genes, and this contribute to generate a stronger immune response (both innate and adaptive) and more frequent autoimmune and inflammatory diseases in female subjects. However, ACE-2 represents the primary route of infection of COVID-19 and it is located on X chromosome. Actions exerted by this enzyme consist not only in the conversion of Angiotensin I, but also in immunomodulation and prevention of lung injury, with a protective effect in female subjects.

Dr. Tiziana Ciarambino

Guest Editor