Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates.

Manning, John T; Fink, Bernhard; Manning, John T.

BACKGROUND The reported national case fatality rates (CFRs) for coronavirus disease 2019 (COVID-19) shows a sex bias with males > females. The relative lengths of the index (2D) and ring (4D) fingers (digit ratio; 2D:4D) is a sexually dimorphic (males < females) proxy of fetal sex steroids (low 2D:4D indicates high prenatal testosterone/low prenatal estrogen). AIM To examine sex-specific relationships of 2D:4D per nation with national values of COVID-19 CFRs. STUDY DESIGN COVID-19 CFRs and the percent of male deaths were related to mean national (self-reported) 2D:4D by sex and hand from a large online survey (the BBC Internet Study). SUBJECTS 103,482 men and 83,366 women. OUTCOME MEASURES Relationships of mean national 2D:4D with CFRs from 41 countries and with national male death rates from 16 countries. RESULTS Male right and left hand 2D:4D showed positive relationships with CFR. These relationships remained significant after removing the influence of female 2D:4D. A positive association of male right and left 2D:4D was detected with the percentage of male deaths. CONCLUSIONS 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).