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

• Published in: Early human development Vol. 146; p. 105074
• Main Authors: Manning, John T., Fink, Bernhard
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.07.2020
• Subjects: ACE2; Adult; Advanced Basic Science; Case fatality rate; Coronavirus; Coronavirus Infections - epidemiology; Coronavirus Infections - ethnology; Coronavirus Infections - mortality; COVID-19; Digit ratio; Ethnicity - statistics & numerical data; Female; Fingers - anatomy & histology; Fingers - growth & development; Humans; Male; Neonatal and Perinatal Medicine; Pandemics; Pneumonia, Viral - epidemiology; Pneumonia, Viral - ethnology; Pneumonia, Viral - mortality; Sex Factors; Testosterone; COVID-19; Testosterone; ACE2; Case fatality rate; Coronavirus; Digit ratio
• DOI: 10.1016/j.earlhumdev.2020.105074
• ISSN: 0378-3782; 1872-6232

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). 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). 103,482 men and 83,366 women. Relationships of mean national 2D:4D with CFRs from 41 countries and with national male death rates from 16 countries. 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. 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). •Digit ratio (2D:4D) is a sexually dimorphic correlate of prenatal sex steroids.•High 2D:4D indicates low prenatal testosterone/high prenatal estrogen.•Relationships of national mean 2D:4D with SARS-CoV2 (COVID-19) case fatality rates were investigated.•Male 2D:4D showed positive relationships with case fatality rates and mortality.•Low prenatal testosterone may be a risk factor for COVID-19 in males.