Increased Risk of Severe COVID Outcomes Identified with Males with Advanced Balding Patterns

Advanced Balding Associated with Increased Likelihood of More Severe Disease Worse Outcomes

A number of studies in 2020 and 2021 have pointed to an increased risk of more severe outcomes in males with COVID 19 compared to women. Several studies have suggested that males with more advanced androgenetic hair loss patterns are at increased of having more severe disease if they do acquire COVID 19.

This interest in studying male balding followed directly from an understanding of how Sars-COV-2 infections lung cells in humans. It is known that the virus infects type II pneumocytes in humans by binding to their surface angiotensin-converting enzyme (ACE-2) receptors. This is done with the help of transmembrane serine protease type 2 (TMPRSS2). The main transcriptional promoters of genes coding TMPRSS2 are androgenic. Theoretically, the elevated level of androgens or androgen receptors would lead to a higher expression of TMPRSS2.

Goren and colleagues were some of the first groups to propose the concept that males with balding are at increased risk for more severe COVID19 outcomes. This study is summarized in the link below.

Early Studies of COVID Severity in Men and Women Androgenetic Alopecia

a) Goren et al. Goren et al first undertook studies in 2020 with 41 male patients with COVID 19. Goren et al observed that 71 % of the patients had advanced balding patterns compared to the 31-53% that would be expected in the general population. This was the start of the interest to better understand if male balding is indeed a risk factor for more severe COVID 19 outcomes.

b) Wambier et al. Wambier et al examined outcomes in 175 patients, including both male and female patients. The group found that patients with advanced AGA were more likely to have severe infection. Severe infections occurred in 70% of male patients and in 30 % of female patients. Wambier et all ultimately proposed the term “Gabrin sign” to denoted balding males that were at higher risk for severe COVID outcomes. Dr Gabrin was the first physician to die from COVID-19 in the United States..
c) Goren et al. A subsequent study of 77 patients by Goren et al also suggested that antiandrogen drugs might reduce disease severity. Males using antiandrogens were less likely to be admitted to the ICU than males who did not use these medications

d) Lee et al. Lee and colleagues also showed that male balding was a risk factor for severe COVID 19 outcomes.

Early Studies of COVID Severity in Women with Hyperandrogenism

a) Cadegiani et al. The authors performed a case–control analysis of 112 female patients in order to measure the incidence of clinical characteristics of COVID- 19 in hyperandrogenic women and showed that women without hyperandrogenic manifestations usually had fewer and less severe symptoms of the COVID-19 infection.

b) Subramaniam et al examined the risk in women with PCOS. They and found that women with PCOS have a 51% higher risk of COVID-19 compared to women without PCOS

It has been proposed that androgens are very relevant to the pathogenesis of COVID 19. It has been shown that androgen regulate two receptors known as transmembrane serine protease (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) receptor. The SARS-CoV-2 uses these receptors to gain access into host cells.

Therefore, higher androgen levels in males may facilitate the entry of Sars-COV-2 into cell.

Ghafoor R et al. 2022

Authors set out to establish the association of androgenetic alopecia (AGA) and the severity of COVID 19 by evaluating 300 hospitalized patients in Karachi, Pakistan with COVID 19.

The researchers basic inclusion criteria included patients of both genders between the age group of 20 to 80 years, who were hospitalized for confirmed COVID-19. with or without AGA, with or without comorbidities, and any duration of disease.

Out of 300 patients, 220 (73.33%) were male and 80 (26.67%) were female.

Male Patients (N=220)

There were 41 (18.6%) males between 20 and 40 years of age, 99 (45%) males between >40 and 60 years of age, and 80 (36.3%) males of age >60 years.

Most males had AGA. Mild-to-moderate Hamilton-Norwood scale (HNS<3) was present in 43 (20%) of males and severe alopecia (HNS3-7) were noted in 177 (80.55%) of males.

Female Patients (N=80)

There were 80 females. 29 (36%) were between the age of 20– 40 years and 51 (64%) were between the age of >40–60 years. There was one female of age >60 years. In females, 43 (54%) had no AGA while 37(46%) had AGA. In 37 females with AGA, mild- to-moderate AGA (Ludwig scale <2) was present in 9 patients (24.32%) and severe alopecia (Ludwig scale 2–3) were seen in 28 (75.68%) patients.

Key Results

Males with severe AGA were more likely to have worse outcomes. This same pattern was not seen in female patients.

The authors pointed out that younger age group of male patients with severe AGA also had adverse outcomes even though they had no known comorbidities. To a lesser degree this finding was also foudn in females with AGA.

Conclusion

The conclusion here is that males are at increased risk for more severe outcomes from COVID - especially those with more advanced balding patterns. These studies continue to fuel the possibility that antiandrogen drugs could help COVID 19.

REFERENCE

Ghafoor R et al. Association of androgenetic alopecia and severity of coronavirus disease 2019. J Cosmet Dermatol 2022 Mar;21(3):874-879.

Goren A, McCoy J, Wambier CG, et al. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020;33(4):e13365.

Wambier CG, Goren A. Severe acute respiratory syndrome corona- virus 2 (SARS-CoV-2) infections is likely to be androgen mediated. J Am Acad Dermatol. 2020;83(1):308-309.

Wambier CG, Goren A, Vano-Galvan S, et al. Androgen sen- sitivity gateway to COVID-19 disease severity. Drug Dev Res. 2020;81(7):771-776.

Wambier CG, Vano-Galvan S, McCoy J, et al. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: the Gabrin sign. J Am Acad Dermatol. 2020;83(2):680-682.

Lee J, Yousaf A, Fang W, Kolodney MS. Male balding is a major risk factor for severe COVID-19. J Am Acad Dermatol. 2020;83(5):353-354.

Muller Ramos P, Ianhez M, Amante MH. Alopecia and grey hair are associated with COVID-19 Severity. Exp Dermatol. 2020;29(12):1250-1252

Wambier CG, Vano-Galván S, McCoy J, Pai S, Dhurat R, Goren A. Androgenetic alopecia in COVID-19: compared to age-matched epidemiologic studies and hospital outcomes with or without the Gabrin sign. J Am Acad Dermatol. 2020;83(6):453-454.

Goren A, Wambier CG, Herrera S, et al. Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men. J Eur Acad Dermatol Venereol. 2021;35(1):e13-e15.

Goren A, Cadegiani FA, Wambier CG, et al. Androgenetic alopecia may be associated with weaker COVID T-cell immune response: an insight into a potential COVID-19 vaccine booster. Med Hypotheses. 2021;146:110439.
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