New Insights in COVID-19 from Dermatological Clues

During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have noted that the virus disproportionately affects men versus women, with the more than 58% of severe cases being experienced by men. Racial differences in disease severity have also been reported. These gender and demographic differences are very similar to those observed in dermatological conditions that are mediated by androgens, for example, androgenetic alopecia (AGA). Our past research in AGA has led us to investigate an association between androgens and COVID-19 pathogenesis.

The connection between COVID-19 and androgens is explained by the mechanism of viral entry into human lung cells. SARS-CoV-2 primarily infects type II pneumocytes and enters host cells by anchoring to the ACE2 cell surface receptor. In order to bind to the receptor, viral surface proteins require modification from another host protein, TMPRSS2. If the amount of TMPRSS2 can be reduced in the lung, the ability of the virus to enter the lung will be attenuated. In humans the TMPRSS2 gene is regulated by the androgen receptor.

As a first step, we have conducted preliminary studies looking for the incidence of androgen mediated hair loss in COVID-19 patients. In a study of 141 COVID patients with severe symptoms, the ratio of hair loss in male COVID-19 patients compared to that of the general male population was 77 to 60 percent, respectively. More interestingly, in females with severe COVID-19, we found 58% had androgenetic alopecia, more than five times higher than in the general female population of the same age.

In our past work we have explored the use of genetic polymorphisms in the androgen receptor gene as a biomarker for susceptibility to androgen mediate disease. We believe that these same biomarkers can be used to identify patients at high risk of severe COVID-19 disease. Similarly, a diagnostic device could be used to identify high-risk individuals within populations with high exposure to the virus, for example, healthcare workers. Currently, we are pursuing two research avenues: 1.) the development and registration of a diagnostic device for COVID-19 susceptibility and 2.) a prophylactic treatment options using existing androgen modulating drugs.

Other Studies

TITLE:

SARS-CoV-2 Environmental Testing Kit

STATUS:

Under development

Publications

Androgen Receptor Genetic Variant Predicts COVID-19 Disease Severity: A Prospective Longitudinal Study of Hospitalized COVID-19 Male Patients.

McCoy J, Wambier CG, Herrera S, Vaño-Galván S, Gioia F, Comeche B, Ron R, Serrano-Villar S, Iwasiow RM, Tayeb MA, Cadegiani FA, Mesinkovska NA, Shapiro J, Sinclair R, Goren A.

J Eur Acad Dermatol Venereol. 2020 Sep 25. doi: 10.1111/jdv.16956. Online ahead of print.

Men infected with SARS-CoV-2 are more likely to be admitted to the intensive care unit (ICU) compared to women.(1) Previously, we have reported that among hospitalized men with COVID-19, 79% presented with androgenetic alopecia (AA) compared to 31-53% that would be expecte …

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Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men.

Goren A, Wambier CG, Herrera S, McCoy J, Vaño-Galván S, Gioia F, Comeche B, Ron R, Serrano-Villar S, Ramos PM, Cadegiani FA, Kovacevic M, Tosti A, Shapiro J, Sinclair R.

J Eur Acad Dermatol Venereol. 2020 Sep 25. doi: 10.1111/jdv.16953. Online ahead of print.

The COVID-19 pandemic has disproportionally affected men.(1) Men infected with SARS-CoV-2 are more than twice as likely to be admitted to the intensive care unit (ICU).(2) This disparity in ICU admissions suggests the important role of androgens in COVID-19 severity …

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Male balding as a major risk factor for severe COVID-19: a possible role for targeting androgens and transmembrane protease serine 2 to protect vulnerable individuals.

Wambier CG, McCoy J, Goren A.

J Am Acad Dermatol. 2020 Sep 11:S0190-9622(20)32600-1. doi: 10.1016/j.jaad.2020.09.015. Online ahead of print.

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Androgen sensitivity in COVID-19 and antiandrogens: Prospective data are still needed.

Ianhez M, Ramos PM, Goren A, Miot HA.

Dermatol Ther. 2020 Aug 9:e14166. doi: 10.1111/dth.14166. Online ahead of print.

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Are night shift workers at an increased risk for COVID-19?

Lim RK, Wambier CG, Goren A.

Med Hypotheses. 2020 Jul 29;144:110147. doi: 10.1016/j.mehy.2020.110147. Online ahead of print.

Recent data has revealed an association between coronavirus disease-19 (COVID-19) incidence and seasonally regulated androgen sensitivity. This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work …

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Androgenetic alopecia in COVID-19: compared to age-matched epidemiologic studies and hospital outcomes with or without the Gabrin sign.

Wambier CG, Vaño-Galván S, McCoy J, Pai S, Dhurat R, Goren A.

J Am Acad Dermatol. 2020 Jul 28:S0190-9622(20)32300-8. doi: 10.1016/j.jaad.2020.07.099. Online ahead of print.

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Spironolactone: An Anti-androgenic and Anti-hypertensive Drug That May Provide Protection Against the Novel Coronavirus (SARS-CoV-2) Induced Acute Respiratory Distress Syndrome (ARDS) in COVID-19.

Cadegiani FA, Wambier CG, Goren A.

Front Med (Lausanne). 2020 Jul 28;7:453. doi: 10.3389/fmed.2020.00453. eCollection 2020.

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Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS).

Cadegiani FA, Goren A, Wambier CG.

Med Hypotheses. 2020 Jul 16;143:110112. doi: 10.1016/j.mehy.2020.110112. Online ahead of print.

In coronavirus disease-19 (COVID-19), four major factors have been correlated with worse prognosis: aging, hypertension, obesity, and exposure to androgen hormones. ...Hence, spironolactone may provide protection from SARS-CoV-2, and has sufficient plausibility to be clini …

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Clock genes may drive seasonal variation in SARS-CoV-2 infectivity: are we due for a second wave of COVID-19 in the fall?

Goren A, Wambier CG, McCoy J, Shapiro J, Vaño-Galván S, Herrera S, Glode LM.

J Biol Regul Homeost Agents. 2020 Jul 16;34(4). doi: 10.23812/20-359-L-35. Online ahead of print.

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Safety Measures in Dermatology Help Minimize Spread of COVID-19.

Goren A, Rathod D, Kroumpouzos G, Jafferany M, Goldust M.

Dermatol Ther. 2020 Jun 7. doi: 10.1111/dth.13773. Online ahead of print.

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Androgenetic Alopecia Present in the Majority of Hospitalized COVID-19 Patients - the "Gabrin sign".

Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard Á, Moreno-Arrones OM, Jiménez-Gómez N, González-Cantero A, Pascual PF, Segurado-Miravalles G, Shapiro J, Pérez-García B, Goren A.

J Am Acad Dermatol. 2020 May 21:S0190-9622(20)30948-8. doi: 10.1016/j.jaad.2020.05.079. Online ahead of print.

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Androgen sensitivity gateway to COVID-19 disease severity.

Wambier CG, Goren A, Vaño-Galván S, Ramos PM, Ossimetha A, Nau G, Herrera S, McCoy J.

Drug Dev Res. 2020 May 15:10.1002/ddr.21688. doi: 10.1002/ddr.21688. Online ahead of print.

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Racial Variations in COVID-19 Deaths May Be Due to Androgen Receptor Genetic Variants Associated with Prostate Cancer and Androgenetic Alopecia. Are Anti-Androgens a Potential Treatment for COVID-19?

McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Müller Ramos P, Washenik K, Andrade M, Herrera S, Goren A.

J Cosmet Dermatol. 2020 Apr 25:10.1111/jocd.13455. doi: 10.1111/jocd.13455. Online ahead of print.

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A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity.

Goren A, Vaño-Galván S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K.

J Cosmet Dermatol. 2020 Apr 16. doi: 10.1111/jocd.13443. Online ahead of print.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated.

Wambier CG, Goren A.

J Am Acad Dermatol. 2020 Apr 10:S0190-9622(20)30608-3. doi: 10.1016/j.jaad.2020.04.032. Online ahead of print.

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What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy.

Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T.

Dermatol Ther. 2020 Apr 1:e13365. doi: 10.1111/dth.13365. Online ahead of print.

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