Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The "Gabrin sign".

To the Editor: Dr Frank Gabrin was the first American physician to die of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection. Dr Gabrin suffered from androgenetic alopecia and was a long-term survivor of bilateral testicular cancer.1 The association between SARS-CoV-2 infectiveness and the androgen pathway has been previously described.2 Androgen-mediated SARS-CoV-2 vulnerability may help explain the disproportioned mortality rate among men.3 We present further epidemiologic evidence that androgen sensitivity might be associated with severe symptoms leading to hospitalization due to COVID-19.
Previously, we reported a possible association between male patients hospitalized with COVID-19 and androgenetic alopecia (AGA); however, the study was limited by its population size of 41 men.4 In this communication, we present additional data from patients with confirmed COVID-19 admitted due to severity criteria (mainly low peripheral oxygen saturation) to 3 tertiary hospitals in Madrid, Spain. The patients were randomly examined by dermatologists who were assisting with the overwhelming number of admitted patients. The study took place from March 23, 2020, to April 12, 2020.
Upon admission, the dermatologists recorded the age, sex, and alopecia diagnosis. Alopecia severity was evaluated using the Hamilton–Norwood scale (HNS) for men and the Ludwig scale (LS) for women. The scores were categorized into groups: “no alopecia” for HNS = 1 or LS = 0; “moderate AGA” for HNS = 2 or LS = 1; and “severe AGA” for HNS >2 or LS >1.
A total of 175 individuals with confirmed COVID-19 were evaluated. Among the patients, 122 were men and 53 were women. Overall, 67% of the patients (95% confidence interval, 60%-74%) presented with clinically relevant AGA. The frequency of AGA in men was 79% (95% confidence interval, 70%-85%) The frequency of AGA in women was 42% (95% confidence interval, 29%-55%). The median age of female patients was 71 years (interquartile range, 22 years). The median age of male patients was 62.5 years (interquartile range, 20 years) (Fig 1, A-
C). Raw data available in Supplement 1 (available via Mendeley at https://data.mendeley.com/datasets/tphxzjkrh8/1). In both sexes, age presented great variation for those with “no alopecia,” whereas those with severe AGA presented an older age distribution and median (Fig 1, D).
The prevalence of age-matched men in a similar white population was estimated to be 31% to 53%,4 whereas in women, the highest AGA prevalence reported (with dermatologist evaluation) was 38% in patients aged >69 years.5 Age group comparison with other references available in Supplement 2 (available via Mendely at https://data.mendeley.com/datasets/jk63cthxbr/2). In our data, 57% of females >69 years old were diagnosed with AGA. These results indicate that a substantial proportion of individuals hospitalized for severe COVID-19 in your centers have AGA.
The hypothesis of androgen-mediated COVID-19 severity requires validation in larger studies. Antiandrogen treatments that could be theoretically studied in the treatment and prophylaxis of severe COVID-19 are indicated in Fig 2
. Therapeutic randomized controlled clinical trials with bicalutamide (NCT04374279), degarelix (NCT04397718), and spironolactone (NCT04345887) are currently underway.
The sample size and lack of a control group and outcomes are limitations of this study. Because dermatologists actively graded AGA, observer bias was possible. The precise AGA rate in an age-matched, not-admitted population with COVID-19 is still unknown to draw further conclusions. Future studies could evaluate whether lung involvement correlates with the severity of AGA or whether the proportion of AGA is higher in intensive care/fatal COVID-19. AGA severity reflects androgen activity over age, which are 2 vulnerability characteristics for COVID-19. AGA is a primary individual characteristic, different from telogen effluvium, which occurs after months of the stress of illness.
Finally, because Dr Gabrin was the first physician to die from COVID-19 in the United States, we propose the use of the eponym the “Gabrin sign” to visually identify patients at higher risk for severe symptoms after COVID-19 infection.