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, Andy; Vañó‐Galván, Sergio; Wambier, Carlos Gustavo; McCoy, J. Philip; Gómez‐Zubiaur, Alba; Moreno‐Arrones, Óscar M.; Shapiro, Jerry; Sinclair, Rodney; Gold, Michael H.; Kovacevic, Maja; Mesinkovska, Natasha Atanaskova; Goldust, Mohamad; Washenik, Ken

doi:10.1111/jocd.13443

Cited by 177 publications

(204 citation statements)

References 16 publications

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“…18,20 In addition, the potential association between androgen level and COVID-19 severity was suggested. 21 Our results also revealed the tendency toward sex difference in the mortality of COVID-19. Further research is needed to assess the effect of sex on the severity of COVID-19.…”

Section: Discussionsupporting

confidence: 64%

Impact of comorbidity burden on mortality in patients with COVID-19: a retrospective analysis of the Korean health insurance database

Cho

Yoon

Lee

2020

Preprint

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We aimed to investigate the impact of comorbidity burden on mortality in patients with COVID-19. We analyzed the COVID-19 data from the nationwide health insurance claims of South Korea. Data on demographic characteristics, comorbidities, and mortality records of patients with COVID-19 were extracted from the database. The odds ratios of mortality according to comorbidities in patients with COVID-19 with and without adjustment for age and sex were calculated. The predictive value of the original Charlson comorbidity index (CCI) and the age-adjusted CCI (ACCI) for mortality in patients with COVID-19 were investigated using the receiver operating characteristic (ROC) curve analysis. Among 7,590 patients with COVID-19, 227 (3.0%) had died. After age and sex adjustment, hypertension, diabetes mellitus, congestive heart failure, dementia, chronic pulmonary disease, liver, renal, and cancer were significant risk factors for mortality. The ROC curve analysis showed that ACCI threshold ≥4 yielded the best cut-off point for predicting mortality (area under the ROC 0.92; 95% CI, 0.91–0.94). Our study revealed multiple risk factors that were associated with mortality in patients with COVID-19. The high predictive power of the ACCI for mortality in our results could support the importance of old age and comorbidities in the severity of COVID-19.

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Section: Discussionsupporting

confidence: 64%

Impact of comorbidity burden on mortality in patients with COVID-19: a retrospective analysis of the Korean health insurance database

Cho

Yoon

Lee

2020

Preprint

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“…Aging, obesity, uncompensated type 2 diabetes mellitus (T2DM), hypertension, male sex, and presence of male androgenetic alopecia (AGA) have been detected as risk factors for COVID-19 complications (1)(2)(3)(4)(5)(6).…”

Section: Covid-19 Is a Multi-systemic Infection Caused By The Severe mentioning

confidence: 99%

Azithromycin with nitazoxanide, hydroxychloroquine or ivermectin, with or without dutasteride, for early stage COVID-19: an open-label prospective observational study in males with mild-to-moderate COVID-19 (The Pre-AndroCoV Male Trial).

Cadegiani

Goren²,

Wambier

et al. 2020

Preprint

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Background: COVID-19 is a multisystemic disorder caused by SARS-CoV-2 that has led to more than 1,000,000 deaths until the end of September 2020. Besides aging, obesity, and metabolic diseases, males, in particular those affected by androgenetic alopecia (AGA), are at higher risk to develop complications. While policies for diagnosis of COVID-19 still focus on the presence of fever or shortness of breath, these symptoms tend to appear only in later and more severe stages of the disease, when viral infectivity is already, hampering potential antiviral approaches. In addition, clinical characterization of early COVID-19 stages still lacks. The objective of the present observational study was to characterize prospectively clinical features and predictors in males during early COVID-19, and to evaluate whether the combination of more sensitive case-detection, early diagnosis and early pharmacological approaches would lead to improved clinical outcomes. Material and methods: Males confirmed for COVID-19 through positive real-time polymerase chain reaction (rtPCR) for SARS-CoV-2 with less than seven days of symptoms and three days of COVID-19 confirmation were divided into non-AGA, AGA not using dutasteride (AGA no-5ARi), and AGA using dutasteride (AGA-5ARi) groups. Patients were actively characterized for baseline and lifestyle characteristics, 22 different diseases, 42 drug classes and vaccines, 26 different symptoms, and 10 different parameters to measure COVID-19 related clinical outcomes. Azithromycin plus hydroxychloroquine, nitazoxanide 500mg or ivermectin, with or without dutasteride or spironolactone were used. Patients were then evaluated for COVID-19 clinical course, duration and progression.Results: A total of 305 males were enrolled, including 192 non-AGA, 71 AGA non-ARi and 52 AGA-5ARi. The prevailing symptoms were anosmia (68.9%), ageusia (61.2%), headache (37.5%), hyporexia (37.5%), fatigue (35.2%), dry cough (35.2%), fever or “feverish” (33.9%), thoracic pain (32.4%), conjunctival hyperemia (29.5%), weakness (29.5%), nasal congestion or rhinorrhea (28.6% and myalgia (26.3%). ARi users remained asymptomatic throughout COVID-19 treatment in 82.7% (43 of 52 males), and the only symptoms present in more than two patients were anosmia and ageusia. Thoracic, upper back, lower back pain, arthralgia affected a higher percentage of AGA no-5ARi than non-AGA males (all p < 0.01), but had similar durations (p = n/s). Anosmia, ageusia, headache, fatigue, myalgia and conjunctival hyperemia were more commonly present and lasted for longer periods in AGA no 5ARi patients (all p < 0.01). Self-reported perception of “sinusitis” and “sore throat”, dry cough and weakness were equally present (p = n/s) but had longer duration in AGA no-5ARi males (all p < 0.01).The different drug were equally distributed. AGA males were more severely affected than non-AGA in terms of duration of clinical manifestations (9.4 ± 6.0 vs 14.2 ± 7.3 days, p < 0.0001) and viral shedding (14.0 ± 5.2 vs 17.8 ± 6.2 days; p < 0.0001), which has been fully mitigated by the chronic use of dutasteride (p < 0.0001 and < 0.0001 vs non-AGA and AGA no-5ARi, respectively, for both clinical manifestations and viral shedding duration. Non-AGA, AGA no-5ARi and AGA-5ARi achieved 95% clinical recovery in seven, 14, and two days, respectively. In regards functional capacity, AGA no -5ARi males at Days 30, 14, 7, and 3 after treatment initiation were similar than non-AGA at Days 14, 7, 3, and 0, respectively (all p > 0.9). None of the patients required hospitalization and mechanical ventilation, or progressed to more severe states. Conclusion: The combination of more sensitive and earlier diagnosis of COVID-19 with a variety of drug combinations with preliminary demonstration of direct or indirect antiviral activity against SARS-CoV-2 demonstrated indisputable improved COVID-19 related clinical outcomes compared to the extensively described COVID-19 clinical course, and avoided the progression to more severe state in all patients included in the present analysis, independently of risk factors, demonstrating that any additional risk factor can be completely mitigated by the combination of more sensitive clinical suspect with early pharmacological approaches.The overwhelming differences indicate that full placebo control RCTs for early COVID-19 may be ethically questionable. Instead, double blind therapies with different options, or mixed open label placebo control for COVID-19 should be considered.

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“…It has also been shown that gender is a prognostic factor, with approximately 60-70% of deaths being in men [5,6], suggesting that steroid hormones may be a contributing factor to the severity of the disease. In further support of this, recent studies have shown that men with male pattern hair loss (caused by elevated androgen signalling [7]), are at higher risk of suffering more severe COVID-19 symptoms [8,9].…”

Section: Introductionmentioning

confidence: 80%

“…This would support the theory that the observed worse prognosis in men following SARS-CoV-2 infection (60-70% of COVID-19-related deaths are in men [5,6]) is at least in part due to elevated expression of TMPRSS2 as a consequence of higher levels of androgen. In light of the recent studies linking male pattern hair loss with more severe COVID-19 symptoms [8,9], it would be of interest to compare TMPRSS2 expression levels in men with and without this androgen-associated form of hair loss.…”

Section: Tmprss2 Expression In the Lung Is Higher In Menmentioning

confidence: 99%

TMPRSS2, required for SARS-CoV-2 entry, is downregulated in lung cells by enzalutamide, a prostate cancer therapeutic

Leach¹,

Isac²,

Bevan³

et al. 2020

Preprint

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The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, attacks various organs but most destructively the lung. It has been shown that SARS-CoV-2 entry into lung cells requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; activation of the androgen receptor increases TMPRSS2 levels in various tissues, most notably the prostate. We show here that treatment with the antiandrogen enzalutamide – a well-tolerated drug widely used in advanced prostate cancer – reduces TMPRSS2 levels in human lung cells. Further, enzalutamide treatment of mice dramatically decreased Tmprss2 levels in the lung. In support of this new experimental data, analysis of existing datasets shows striking co- expression of AR and TMPRSS2, including in specific lung cell types that are targeted by SARS- CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

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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

Abstract: A preliminary observation of high frequency of male pattern hair loss among admitted COVID-19 patients and suggest that androgen expression might be a clue to COVID-19 severity.

Cited by 177 publications

References 16 publications

Impact of comorbidity burden on mortality in patients with COVID-19: a retrospective analysis of the Korean health insurance database

Impact of comorbidity burden on mortality in patients with COVID-19: a retrospective analysis of the Korean health insurance database

Azithromycin with nitazoxanide, hydroxychloroquine or ivermectin, with or without dutasteride, for early stage COVID-19: an open-label prospective observational study in males with mild-to-moderate COVID-19 (The Pre-AndroCoV Male Trial).

TMPRSS2, required for SARS-CoV-2 entry, is downregulated in lung cells by enzalutamide, a prostate cancer therapeutic

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