Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul:146:105074.
doi: 10.1016/j.earlhumdev.2020.105074. Epub 2020 May 14.

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

John T Manning  1 , Bernhard Fink  2
Affiliations

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

John T Manning et al. Early Hum Dev. 2020 Jul.

Abstract

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).

Keywords: ACE2; COVID-19; Case fatality rate; Coronavirus; Digit ratio; Testosterone.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The relationship between male mean right digit ratio per nation and log-transformed national case fatality rate (log CFR) in 41 nations. Note: y = −45.33 + 46.53 ∗ x; r2 = 0.12.
Fig. 2
Fig. 2
The relationship between mean male right 2D:4D per nation and the national percentage of male deaths in 16 countries. Note: y = −1787.10 + 1880 ∗ x; r2 = 0.40.
See this image and copyright information in PMC

Comment in

References

    1. Shi Y., Yu X., Zhao H., Wang H., Zhao R., Sheng J. Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Crit. Care. 2020;24:108. doi: 10.1186/s13054-020-2833-7. - DOI - PMC - PubMed
    1. Guan W.-J., Ni Z.-Y., Hu Y., Liang W., Ou C.-Q., He J.-X. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020 doi: 10.1056/NEJMoa2002032. - DOI - PMC - PubMed
    1. Channappanavar R., Fett C., Mack M., Ten Eyck P.P., Meyerholz D.K., Perlman S. Sex-based differences in susceptibility to coronavirus infection severe acute respiratory syndrome. J. Immunol. 2017;198:4046–4053. doi: 10.4049/jimmunol.1601896. - DOI - PMC - PubMed
    1. Klein S.L., Flanagan K.L. Sex differences in immune responses. Nat. Rev. Immunol. 2016;16:626–638. doi: 10.1038/nri.2016.90. - DOI - PubMed
    1. Rettew J.A., Huet-Hudson Y.M., Marriott I. Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol. Reprod. 2008;78:432–437. doi: 10.1095/biolreprod.107.063545. - DOI - PubMed