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Review
. 2021 Jan;71(1):3-8.
doi: 10.1007/s12020-020-02536-6. Epub 2020 Nov 11.

Sex differences in COVID-19: the role of androgens in disease severity and progression

Mohamed S Mohamed  1 , Thiago C Moulin  2 , Helgi B Schiöth  1   3
Affiliations
Review

Sex differences in COVID-19: the role of androgens in disease severity and progression

Mohamed S Mohamed et al. Endocrine. 2021 Jan.

Abstract

Purpose: Throughout the SARS-CoV2 pandemic, multiple reports show higher percentages of hospitalization, morbidity, and mortality among men than women, indicating that men are more affected by COVID-19. The pathophysiology of this difference is yet not established, but recent studies suggest that sex hormones may influence the viral infectivity process. Here, we review the current evidence of androgen sensitivity as a decisive factor for COVID-19 disease severity.

Methods: Relevant literature investigating the role of androgens in COVID-19 was assessed. Further, we describe several drugs suggested as beneficial for COVID-19 treatment related to androgen pathways. Lastly, we looked at androgen sensitivity as a predictor for COVID-19 progression and ongoing clinical trials on androgen suppression therapies as a line of treatment.

Results: SARS-COV2 virus spike proteins utilize Transmembrane protease serine 2 (TMPRSS2) for host entry. Androgen receptors are transcription promoters for TMPRSS2 and can, therefore, facilitate SARS-COV2 entry. Variants in the androgen receptor gene correlate with androgen sensitivity and are implicated in diseases like androgenetic alopecia and prostate cancer, conditions that have been associated with worse COVID-19 outcomes and hospitalization.

Conclusion: Androgen's TMPRSS2-mediated actions might explain both the low fatalities observed in prepubertal children and the differences between sexes regarding SARS-COV2 infection. Androgen sensitivity may be a critical factor in determining COVID-19 disease severity, and sensitivity tests can, therefore, help in predicting patient outcomes.

Keywords: CAG repeats; Dexamethasone; Hydroxychloroquine; Nitric oxide; SARS-COV2; Testosterone.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Androgens facilitate SARS-COV2 entry through a TMPRSS2-mediated pathway. Both androgen receptor and ACE2 genes are located on chromosome X. Circulating androgens binds to AR, activating it, which promotes TMPRSS2 transcription. SARS-CoV2 spike proteins are then primed by TMPRSS2, allowing the interaction with ACE2 receptors to enter host cells
Fig. 2
Fig. 2
Theoretical mechanisms suggesting CAG repeats length and associated androgen sensitivity as a predictor for COVID-19 disease severity
See this image and copyright information in PMC

References

    1. R. Castagnoli, M. Votto, A. Licari, I. Brambilla, R. Bruno, S. Perlini et al. Severe Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatrics. American Medical Association, 882–889 (2020). 10.1001/jamapediatrics.2020.1467 - PubMed
    1. N. Sharifi, C.J. Ryan Editorial: Androgen hazards with COVID-19. Endocrine-Related Cancer. BioScientifica Ltd.; 2020. E1–E3. 10.1530/ERC-20-0133 - PubMed
    1. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection. J. Immunol. 2017;198:4046–4053. doi: 10.4049/jimmunol.1601896. - DOI - PMC - PubMed
    1. C.G. Wambier, A. Goren, S. Vaño-Galván, P.M. Ramos, A. Ossimetha, G. Nau et al. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Res. Wiley-Liss Inc.; 2020. 10.1002/ddr.21688 - PMC - PubMed
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–280.e8. doi: 10.1016/j.cell.2020.02.052. - DOI - PMC - PubMed

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