Gender variations in COVID-19 mortality might be (at least partially) explained by estrogen. Channappanavar (2017) suggests that sex differences in the susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females. I know that mice are not people, and that SARS-CoV is not SARS-CoV2, but the similarities might warrant further research.

Article Sex-Based Differences in Susceptibility to Severe Acute Resp...

We are still learning about this virus. One preprint study shows that men are more susceptible.

Jian-Min Jin, et al. Gender differences in patients with COVID-19: Focus on severity and mortality doi: https://doi.org/10.1101/2020.02.23.20026864. available at

https://www.medrxiv.org/content/10.1101/2020.02.23.20026864v2

Another comprehensive article in NYTimes discusses the complex nature of it -

https://www.nytimes.com/2020/04/03/us/coronavirus-male-female-data-bias.html

Part of what makes the Covid-19 pandemic so unnerving is that it’s hard to know how the virus will affect any individual person. Though most people infected with the coronavirus—81%, according to the US Centers for Disease Control and Prevention (CDC)—will present with few or mild symptoms, others may find themselves relying on a ventilator to breathe, or no longer breathing at all.

Talking about gender differences in response to virus, we need to keep in mind the previously proven immunomodulatory effect of progesterone. Many inflammatory diseases improve in pregnant women. Progesterone can modulate immune response not only trough progesterone receptors, but also via glucocorticoid receptors.

Progesterone suppresses the lipopolysaccharide-induced pro-inflammatory response in primary mononuclear cells isolated from human placental blood.

Progesterone modulates the T-cell response via glucocorticoid receptor-dependent pathways.

In my unpublished work progesteron knock out mice showed aggravated imflammation, and they even lost resistance to some pathologies.

In terms of increased muscle mass, it is possible that higher amount of pregnenolole (shared precursor for all steroids) is direceted toward and spend for testosterone synthesis, so progesterone could became depleted.

Another possible contribution to sex differences in the susceptibility to SARS-CoV-2, is that ACE2-expression is dramatically reduced with ageing, more so in men than women (ACE2 is located on the X chromosome).

Sex hormones, ACE2 expression, and other associated factors as a cause of gender differences in morbidity and mortality due to COVID-19.

Higher infection rate and mortality due to COVID-19 in males compared with females is due to an interplay of sex hormones (Estrogen, Progesteron, and Testosterone) and associated diseases along with ACE2 receptor expression and the smoking prevalence and related diseases in men compared with women.

Preprint Sex Differences in Severity and Mortality Among Patients Wit...

Article Testosterone, a key hormone in the context of COVID-19 pandemic

Preprint ACE2 and TMPRSS2 variants and expression as candidates to se...

Preprint ACE2 Expression is Increased in the Lungs of Patients with C...