key: cord-0921959-0pwgzeec
authors: Wambier, Carlos Gustavo; McCoy, John; Goren, Andy
title: 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
date: 2020-09-11
journal: J Am Acad Dermatol
DOI: 10.1016/j.jaad.2020.09.015
sha: dd7abcd94100c003f457ff0fdc33a566e6a88401
doc_id: 921959
cord_uid: 0pwgzeec

nan

United States. 7 2 Applied Biology, Inc. Irvine, CA, United States 8 9

*twitter handle @WambierMD 10 11 Tables: 0  27 Supplementary tables: 0 28

Keywords: COVID-19; SARS-CoV-2; Gabrin sign; vulnerability; androgen receptor; androgenetic 29 alopecia; anti-androgen therapy; transmembrane protease serine 2; TMPRSS2; Dutasteride; 7. 2 They further demonstrated in multivariate logistic regression that very severe baldness had 41 a higher odds-ratio for COVID-19 positivity than hypertension, dyslipidemia, diabetes, obesity 42 per body mass index, or age. 1 It is noteworthy that severe baldness was reported to be a better 43 predictor of test positivity than obesity, as there are many reports linking obesity to COVID-19 44 disease severity. 3 This underscores the need for further studies and to communicate these 45 findings beyond the dermatology community. 46

In the context of symptomatic presentations reported in Lee et al., the baldness survey was 47 conducted many years ago. Some patients who initially self-reported as having frontal baldness 48 or vertex baldness (patterns 2 or 3, respectively) could have developed pattern 4 by 2020. 49 Therefore, we believe the numbers with "very severe baldness" may be even greater than what 50 was reported. The main evidence of vulnerability is the clinical outcome during the course of 51 COVID-19, particularly intensive care unit (ICU) admission and fatality rates. Severe baldness, 52 the Gabrin sign (NHS=3-7), has been associated with both increased ICU admissions and 53 increased death rates. 2 54

Understanding the mechanisms leading to host susceptibility provides an opportunity for 55 pharmacological interventions to protect vulnerable individuals. We have proposed that 56 androgen sensitivity is associated with SARS-COV-2 infection, possibly, through androgen-57 promoted transmembrane protease serine 2 (TMPRSS2). 4 Recently, results of a study using 58 J o u r n a l P r e -p r o o f bromhexine hydrochloride, a common cough over-the-counter medication only available 59 outside the United States were reported. Bromhexine was the first drug identified to be a 60 TMPRSS2 inhibitor. The open-label randomized, standard protocol-controlled trial enrolled 78 61 patients for treatment of clinical and radiologic pneumonia suspected to be due to COVID-19. 5 62

The arm with bromhexine was superior to the standard protocol, with only 2 patients admitted 63

to the ICU and 0 deaths versus 11 patients admitted to the ICU (p=0.006) and 5 deaths in the 64 standard protocol arm (p=0.027). 5 65

Reduced expression of TMPRSS2 is also achieved by blocking androgens with medications 66 commonly used in dermatology. 4 Results of our recent COVID-19 prospective cohort study 67 involving 77 hospitalized men were also particularly encouraging: Only 1 out of 12 individuals 68 were admitted to the ICU (8%) in the cohort of men using 5-alpha-reductase inhibitors or other 69 anti-androgen drugs (dutasteride=9, finasteride=2, and spironolactone=1), versus 38 out of 65 70 men (58%) not taking anti-androgens (p=0.0015). The full study is currently under peer review, 71 raw data available at https://data.mendeley.com/datasets/6gpc32dyy7/2. 72

Medications that target TMPRSS2 have demonstrated improved COVID-19 outcomes in clinical 73 studies, and have the potential to protect vulnerable individuals during the pandemic. We hope 74 that in the near future more data will be available regarding interventions focused on inhibiting 75 host factors that increase susceptibility to SARS-COV-2, such as the androgen-TMPRSS2 76 pathway. 77 78 J o u r n a l P r e -p r o o f

Male Balding is a Major Risk Factor for Severe 80

COVID-19: compared to age-matched epidemiologic studies and hospital outcomes with 83 or without the Gabrin sign

Individuals with obesity and COVID-19: A global 86 perspective on the epidemiology and biological relationships

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 89 infection is likely to be androgen mediated

Effect of bromhexine on clinical outcomes and 92 mortality in COVID-19 patients: A randomized clinical trial