Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The “Gabrin sign”
Authors: Carlos Gustavo Wambier, Sergio Vaño-Galván, John McCoy, Alba Gomez-Zubiaur, Sabina Herrera, Ángela Hermosa-Gelbard, Oscar M. Moreno-Arrones, Natalia Jiménez-Gómez, Alvaro González-Cantero, Pablo Fonda-Pascual, Gonzalo Segurado-Miravalles, Jerry Shapiro, Bibiana Pérez-García, Andy Goren
Journal: Journal of the American Academy of Dermatology (2020)

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.1Gabrin F.D. Discovering the 'heart of care'.Med Econ. 2012; 89: 20-23PubMed Google Scholar The association between SARS-CoV-2 infectiveness and the androgen pathway has been previously described.2Wambier C.G. Goren A. SARS-COV-2 infection is likely to be androgen mediated.J Am Acad Dermatol. 2020; 83: 308-309Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Androgen-mediated SARS-CoV-2 vulnerability may help explain the disproportioned mortality rate among men.3Richardson S. Hirsch J.S. Narasimhan M. et al.Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area.JAMA. 2020; 323: 2052-2059Crossref PubMed Scopus (6528) Google Scholar 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.4Goren A. Vaño-Galván S. Wambier C.G. et al.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.J Cosmet Dermatol. 2020; ([e-pub ahead of print])https://doi.org/10.1111/jocd.13443Date accessed: May 10, 2020Crossref Scopus (149) Google Scholar 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%,4Goren A. Vaño-Galván S. Wambier C.G. et al.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.J Cosmet Dermatol. 2020; ([e-pub ahead of print])https://doi.org/10.1111/jocd.13443Date accessed: May 10, 2020Crossref Scopus (149) Google Scholar whereas in women, the highest AGA prevalence reported (with dermatologist evaluation) was 38% in patients aged >69 years.5Birch M.P. Messenger J.F. Messenger A.G. Hair density, hair diameter and the prevalence of female pattern hair loss.Br J Dermatol. 2001; 144: 297-304Crossref PubMed Scopus (242) Google Scholar 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. The authors are grateful to Andrew Messenger, MD, FRCP (University of Sheffield, U.K.) and Rodney Sinclair, MBBS, MD, FACD (University of Melbourne, Australia) for the suggestion of and collaboration with Supplement 2. Male balding is a major risk factor for severe COVID-19Journal of the American Academy of DermatologyVol. 83Issue 5PreviewTo the Editor: Recent observations by Wambier et al1 suggest that men with pattern baldness are at high risk for severe symptomatic COVID-19 infection. Two preliminary studies1,2 noted high rates of androgenic alopecia in men hospitalized for severe COVID-19. Both of these uncontrolled observational studies were limited by small sample size. To further evaluate this intriguing observation, we examined severity of hair loss in 1941 hospitalized male patients tested for COVID-19 using data from the UK Biobank. Full-Text PDF Comment on "Androgenetic alopecia present in the majority of patients hospitalized with COVID-19"Journal of the American Academy of DermatologyVol. 84Issue 1PreviewTo the Editor: We read with great interest the article in which Wambier et al1 observed a correlation of androgenetic alopecia (AGA) and COVID-19 severity. However, we found some inaccuracies in the analysis and would like to clear them up. Full-Text PDF Androgenetic alopecia in COVID-19: Compared to what?Journal of the American Academy of DermatologyVol. 83Issue 6PreviewTo the Editor: In a timely study certain to attract considerable attention, Wambier et al1 propose an association between androgenetic alopecia (AGA) and severe manifestations of coronavirus disease 2019 (COVID-19). In a cohort of patients hospitalized with COVID-19, they find AGA prevalence of 79% in men and 42% in women, citing other literature to argue these rates exceed expectation. Unfortunately, in the absence of additional clarification, the literature cited does not appear to support this claim. Full-Text PDF