No credible evidence for links between 2D:4D and COVID-19 outcomes: A probabilistic perspective on digit ratio, ACE variants, and national case fatalities

Abstract

Research into COVID-19 susceptibility and outcomes are critical, but claims must be carefully evaluated to inform policy decisions. In a recent series of articles, Manning and Fink [1–3] use national-level data to describe associations between case-fatality ratios and male and female finger ratios (2D:4D), a suggested measure of prenatal androgen exposure, as well as angiotensin-converting enzyme (ACE) allele and genotype frequencies. The authors suggest that 2D:4D is linked with ACE variant prevalence, and that higher male 2D:4D is associated with higher case fatality ratios, and point to 2D:4D as a useful prognostic measure for COVID-19 susceptibility. A critical review and robust Bayesian analysis of the hypothesis is described here, finding no conclusive evidence of COVID-19 mortality and 2D:4D, nor associations between 2D:4D and ACE1 allele or ACE2 genotype frequency. This absence of evidence is present for data taken from the second wave of COVID-19 in October 2020. Problematic theoretical grounding, individual-level conclusions drawn from national-level data, and issues with statistical inference in the original articles are discussed. Taken together, the current data offer no clear utility of 2D:4D in determining COVID-19 outcomes.

Digit ratios and their asymmetries as risk factors of developmental instability and hospitalization for COVID-19

“…There is considerable support for the link between 2D:4D and prenatal sex steroids 13 but for a contrasting view see McCormick & Carre, 2020 14 . Manning and Fink found that nations with high CFR’s had high mean male 2D:4D 9 , thus supporting the hypogonadal theory (in support see Sahin, 2020 and for a critical view see Jones et al, 2020 15 , 16 ). With regard to right–left asymmetry of 2D:4D, i.e.…”

Insights into the Scenario of SARS-CoV-2 Infection in Male Reproductive Toxicity

“…These variations in androgen levels have been seen in the patients treated with ADT in prostate cancer treatment [ 112 , 113 , 119 , 120 ]. According to statistics from around the world, males are more likely to contract SARS-CoV-2 coronavirus infections than females.…”

“…AGA is caused due to the higher androgen levels in the hair follicles as it results in the formation of dihydrotestosterone. In young individuals, severe steroid intake causes hyperandrogenization [ 119 , 124 ]. Adrenal androgens have not yet been considered when studying how androgens affect SARS-CoV-2 infections because they make up a small portion of all androgens and can change throughout the illness, particularly when dexamethasone is administered [ 125 ].…”