Graphical abstract
Key words: 5-α reductase, ACE2, androgen receptor, androgenetic alopecia, angiotensin converting enzyme 2, COVID-19, dutasteride, finasteride, human skin, retinoids, antiandrogen therapy, SARS-CoV-2, TMPRSS2, transmembrane protease serine 2
Coronavirus disease 2019 (COVID-19) pandemic fatalities are rare before adrenarche/puberty (<10 years of age), and the vulnerability of males to severe disease1 has been constantly reported over the past months of pandemic.
The first biologic step required for potential infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the priming of the spike proteins by transmembrane protease, serine 2 (TMPRSS2). Although other proteases have been described to activate the spikes in vitro, only TMPRSS2 activity is regarded as essential for viral spread and pathogenesis in the infected hosts.2 TMPRSS2 may also cleave angiotensin converting enzyme 2 (ACE2) for augmented viral entry.3
Androgen receptor activity has been considered a requirement for the transcription of the TMPRSS2 gene because no other known TMPRSS2 gene promoter has been described in humans to date.4 , 5
Male vulnerability may be further enhanced by X-linked inheritance of genetic polymorphisms (androgen receptor and ACE2 genes loci are in chromosome X). Obvious dermatologic signs of hyperactivation of androgen receptors are pattern reduction of density of scalp hair, increased density of facial and chest hair, acne, and oily skin. Theoretically, the hyperandrogenic phenotype might correlate with COVID-19 increased viral load, increased viral dissemination, and severity of lung involvement (Infographic 1 ).
Infographic 1.
Androgen-mediated COVID-19.
Studies are still required for epidemiologic conclusions. Acknowledging the importance of androgens during the COVID-19 pandemic may offer another targeted therapy for trials, with androgen suppression to reduce host vulnerability when infection risk is high.
Footnotes
Funding sources: None.
Conflicts of interest: None disclosed.
IRB approval status: Not applicable.
References
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