A: Most likely due to biological sex differences in immune function, though other social and behavioral factors may contribute as well.
Sadly, men are more likely be hospitalized, admitted to the ICU, and die from COVID-19 than women. This pattern first emerged in China and has been relatively consistent across countries, supporting the notion of important biological differences in immune response (as opposed to differences in smoking for instance).
In general, females have a more robust immune response starting from birth, when male infant mortality due is significantly higher than females. One trade-off is that women have higher rates of illness associated with over-active immune systems such as allergic and autoimmune diseases.
Sex differences in several aspects of immune response relative to SARS-CoV-2 have been identified, including initial innate immune responses and the immune-regulating roles of sex hormones such as estrogen and testosterone.
Androgens-male hormones such as testosterone-appear to boost the virus’ ability to get inside cells. In a recent study, prostate cancer patients who were receiving androgen-deprivation therapy as part of their treatment had significantly lower risk of SARS-CoV-2 infection compared to prostate cancer patients not receiving this therapy.
In previous outbreaks of coronaviruses (SARs-CoV and MERS-CoV), males also showed increased infection incidence and severity. In the lab, male mice show increased susceptibility to SARS-CoV including elevated viral titers and more inflammation in the lungs.
While these differences in immune response are important, there are likely interactions with other risk factors for men including higher rates of smoking and drinking, lower frequency of hand-washing, and delays in seeking medical attention. Men also have higher rates of co-morbidities such as cardiovascular and lung disease that put them more at risk for COVID-19 complications.
Gender differences in who gets infected are less consistent across countries because this often depends on social context, including gendered aspects of occupations and who is able to socially distance. Women for instance make up 76% of frontline healthcare workers in the EU. A recent paper showed that the gender differences in infection vary with age, with women more likely to be infected during working ages while men make up more cases at older ages.
Bottom line, being male (especially aged 60+) does increase risks of COVID-19 complications and mortality.
We LOVE our Nerdy Boys, so guys PLEASE use this opportunity to close the gender gap in preventive behaviors such as hand-washing, mask wearing, and social distancing. You can’t change your immune system, but you can dramatically reduce your chances of getting infected!
UPDATE: Also see this new pre-print by Dr. Akiko Iwaski and colleagues: Tl;DR: women develop more robust T- cell response to SARs-CoV-2 than men.
Additional resources:
Global health 50/50 is a great resource for sex-specific COVID-19 data across countries:
Sex differences in infant and overall mortality
Review of sex differences in respiratory infections
