Day 121: Estrogen Again

PlagueBlog readers may recall some rather ill-thought-out attempts to make male coronavirus patient survival rates more like female ones by administering estrogen. Perhaps the publication of a different sort of estrogen result will dampen that enthusiasm: Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates (in Early Human Development Volume 146, July 2020).

To make a long finger short, everyone tends to have slightly shorter index than ring fingers (as measured from the crease), but men's are proportionally shorter than women's, given them a lower 2D:4D ratio on average. This difference has previously been shown to result from exposure to testosterone or estrogen in the womb, and the effect is stronger for the right hand.

Digit ratio is perhaps most memorable for its erstwhile association with homosexuality. It seems to have held onto the correlation between low ratios (extra-short index fingers) and lesbianism, while the correlation between high ratios (unusually long index fingers) and male homosexuality is now in doubt. Digit ratio has also been connected to an assortment of personality traits as well as some sex-specific cancers. However, it does not correlate with adult testosterone levels. It is worth noting as well that cross-ethnic differences in digit ratios can be bigger than the male/female difference, though these differences are still thought to be genetic.

The latest correlation with digit ratio is, of course, COVID-19 outcomes. Sadly, the paper involves no direct measurements of patients. Rather, in the tradition of the not-so-well-received vaccine theories, the authors dig up mean national digit ratios for a host of nations and compare them to case fatality rates (CFR) by sex:

At the national level, high mean 2D:4D (indicating low prenatal testosterone/high prenatal estrogen) is associated with high CFRs and percent male mortality. At the individual level, high 2D:4D may be a risk factor for severity of COVID-19 in males. We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).

ACE2 expression is associated with healthy sex hormone levels in either sex, and, while a route of entry for the virus, ACE2 is also a defense against it. The authors' reasoning on this point seems to rely on hypogonadism being an ongoing effect of high digit ratio in men, but it's not (yet another reason not to try to correct the problem of maleness in the ICU). Nevertheless their speculation about ACE2 or ACE2-analogue replacement therapy as a treatment for coronavirus is interesting.

Massachusetts case counts are up 0.7% today. There appears to be a growing inverse relationship between mask compliance and ambient temperature. (Lock up your grandmas, folks; it's summertime!)