SARS-CoV-2 & androgenic alopecia: exploring links!

Dear Editor,

The novel coronavirus presented with a spectrum of clinical presentations involving multiple organs and organ systems. These ranged from mild flu and cough to the more severe multiorgan failure, requiring intensive care monitoring. Among these clinical vignettes, cutaneous clinical manifestations, although not life‐threatening, did appear as a surprise to the clinicians. In this letter, we discuss the pathophysiological mechanism of this presentation ‐ both molecular and environmental ‐ and discuss the impact antiandrogenetic alopecia medicines have on the treatment of SARS‐CoV‐2.

Androgenetic alopecia is the main form of scalp hair loss affecting 60–70% of the population. It is characterized by the miniaturization of large, thick, pigmented terminal hair with a diameter of >0.03 mm to thin, fine, nonpigmented vellus hair with a diameter of <0.03 mm. This is because of the early entrance of the hair follicle into the catagen phase and the lag in the transition from the telogen phase to the anagen phase, resulting in the reduction of the anagen phase.

SARS‐CoV‐2 has shown a spectrum of clinical dermatological manifestations, in both hospitalized and nonhospitalized patients, androgenetic alopecia areata (AA) being a predominant presentation. The viral disease is dependent on the binding of viral spike (S) protein to the angiotensin‐converting enzyme 2 (ACE‐2) and transmembrane protease serine 2 (TMPRSS2)‐mediated cleavage of the S‐protein resulting in viro‐cellular membrane fusion, and entry of the virus into the host cell. Moreover, TMPRSS2 activity has shown to cleave ACE‐2, augmenting the viral entry of SARS‐CoV‐1. Studies have shown that only androgen receptor activity is required for the transcription and regulation of TMPRSS2 in nonprostatic tissues including the lung and scalp.

With an underlying pathophysiological explanation, the observations of an increased incidence of AA globally linked to SARS‐CoV‐2 became evident. Kutlu and colleagues reported that the density of AA patients in May 2020 was significantly higher than last year, i.e., May 2019. Similarly, Goren and colleagues demonstrated a higher prevalence of androgenetic AA in hospitalized SARS‐CoV‐2 patients than would be expected from the same population. A brief literature review of available data is shown in Table 1.

Table 1

Literature review of AA patients

Study authors	Number of cases reported	Mean age of patients (years)	Gender distribution (M/F)	Region of reporting	Notable findings
Andy Goren et al. 5	41	58	♂: 41 ♀: 0	Spain	Of the 41 patients admitted with SARS‐CoV‐2, 29 (71%) were diagnosed with clinically significant androgenetic AA (HNS > than 2) and 12 (29%) had clinically irrelevant relevant signs of androgenetic AA (HNS scale 1 or 2). About 16 (39%) were classified as severe androgenetic AA (HNS 4‐7).
Carlos Gustavo Wambier et al. 8	175	♂: 62.5 ♀: 71	♂: 122 ♀: 53	Spain	Overall, 67% of the SARS‐CoV‐2 patients presented with clinically relevant androgenetic AA. The frequency of androgenetic AA in men was 79% and in women was 42%. In age‐matched women of a similar population, the highest androgenetic AA prevalence reported was 38% in patients aged > 69 years. However, in their SARS‐CoV‐2 females, >69 years, 57% were diagnosed with androgenetic AA.
Dursen Turkmen et al. 9	563	33.4	♂: 316 ♀: 247	Turkey	During the pandemic, TE was seen in 27.9% of the patients, SAA was seen in 2.8%, FAA was seen in 2.5%, and SD was seen on the scalp in 19.9%. It was found that TE was statistically significantly higher in female patients when compared with male patients before and during the pandemic.

AA, Alopecia Areata; FAA, Facial Alopecia Areata; HNS, Hamilton‐Norwood Scale; SAA, Scalp Alopecia Areata; SD, Seborrheic Dermatitis; TE,Telogen Effluvium.

Even though molecular biology explains the occurrence of androgenetic AA in SARS‐CoV‐2, scientists believe that a stress‐prone SARS‐CoV‐2 period, including travel restrictions and social distancing, is partially responsible for hair fall. Kutlu and colleagues explain the vicious cycle between psychiatric disorders and AA, whereby increased stress & depression (S&D)‐driven emotional toll can increase the incidence of AA, and accelerated hair fall could consequently lead to S&D.

Multiple studies have used anti‐AA medicines to both treat alopecia and decrease the severity of SARS‐CoV‐2. Spironolactone, for instance, has proven to be an excellent prophylactic candidate for the prevention of SARS‐CoV‐2. This drug increases the levels of circulating ACE‐2, downregulates the TMPRSS2 gene, and mitigates the incidence of obesity‐linked SARS‐CoV‐2 complications. In addition to the above‐mentioned points, and spironolactone's inherent anti‐inflammatory & antiviral nature, this agent could have a useful impact in avoiding the pulmonary impact of SARS‐CoV‐2.

Similarly, given the androgen‐mediated SARS‐CoV‐2 pathogenesis, nonsteroidal androgen receptor blockers, such as finasteride, have gained popularity to treat AA and the coronavirus infection, especially given the safe drug profile it carries. Perhaps, what's been more attractive is the prospective use of Cepharanthine (CEP), a naturally occurring alkaloid and an essential component of AA treatment in traditional Japanese medicine. CEP suppresses all major components of viral replication and inflammation, including downregulation of nuclear factor‐kappa B, and limiting the production of nitric oxide, and cytokines, thereby inhibiting SARS‐CoV‐2's entry and replication in the host cell.

In the end, even though AA does not pose a threat to the physical wellbeing of an individual or accelerate the disease process, the mental and social impact of hair fall can downplay the health‐related quality of life of an individual. General physicians and dermatologists should counsel their patients and raise awareness in order to decrease the mental burden in an already stress‐prevalent time.