COVID19, sex and gender - an update from Italy

Some new data and ideas for potential mechanisms

1. The data

We have now official data, published by Istituto Superiore di Sanita’(ISS) on 21,551 SARS-CoV-2 patients dying in Italy up to April 20th

- Men were 64.2% of all deaths -> confirming the male bias of the virus seen worldwide 

- comorbidities were equally split between men and women, with sex-specific comorbidities emerging -> diseases more common in men such as COPD, ischemic heart disease and chronic liver disease should be further investigated

- Before hospitalization, 24% of SARS-CoV-2 positive deceased patients (for which we have chart reviews available, n=1,890) followed ACE-inhibitor therapy and 16% angiotensin receptor blockers-ARBs therapy -> no clear link to ACE treatment so far

- Fever and dyspnea were again the most common symptoms, but no breakdown by sex was provided. In contrast, this analysis has been performed in the Spanish cohort, revealing for instance that GI symptoms are more common in women (thanks to @Florencia Iulita for bringing this to my attention) -> there are reasons to believe that symptoms present differently in men and women, which might account for some missed diagnosis in women

2. Wait but why?

As a further confirmation of the importance of the topic, ISS has released a statement on the gender differences observed in #COVID19 infection, suggesting three potential mechanisms: 1. Smoke, 2. Hygiene, 3. Immunity pathways. This is my take:

1. Smoke is only slightly more common in men (29.9%) than women (21.6%)  in Italy, according to recent estimates. The difference is driven by the oldest age brackets, over 65,  while in middle aged women, smoking rates are comparable to men.  In addition,  in a recent study with high-school students, it turned out that more girls (24%) than boys (16%) smoke. While smoke might have a role in other countries, I do not think it's a major player in Italy. We need epidemiological data to show the incidence of smokers amongst death cases, split by sex.
2. Hygiene -assuming women really do present a more robust and frequent habit of self-care and self-hygiene (which I doubt)- should impact infection more than mortality. Let's assume women wash their hands more frequently than men, this should result in dramatically fewer infection cases amongst women. In contrast, infection rates are equal across sexes, worldwide. Let's not get even started on the hygiene of children, who, yet, seem to be protected against the virus.
3. The most likely explanation for sex differences in COVID19 lies in the different regulation of the immune system and, linked to this, the preexisting comorbidities. These are complex issues which will require extensive epidemiological, clinical and basic research. The role of chromosome X inactivation (including the fact that the gene for ACE2 is an 'escaper'), the expression of key immune modulators in men and women before and after treatments, levels of viral receptors in lungs and other tissues of men and women, all these need to be clarified in robust, peer reviewed publications.

The most likely explanation for sex differences in COVID19 lies in the different regulation of the immune system

We need a global concerted research effort to elucidate these points -towards #precisionmedicine, #womensbrainpro.

If you are interested in this topic, here a webinar WBP recently organised; here a post written by the Society for Women's Health Research, to which WBP contributed, and here an interview by WBP cofounders (in Italian).