Hair disorders associated with post-COVID-19 infection in females: a cross-sectional study

Background Coronavirus disease (COVID-19) currently named SARS-CoV-2 is a contagious disease caused by a coronavirus. The virus may infect the hair follicles directly or indirectly through systemic changes in the immune or hormonal systems. Aims In the current study we aimed to determine the prevalence of hair disorders in females infected with COVID-19. Methods Data was collected using a questionnaire covering four main domains: personal data, past medical history, COVID-19 history and treatment, and existence of any hair problems and their management. No identifier or sensitive data were collected. Those complaining of hair loss were subjected to complete general and local hair examination using trichoscopy to confirm hair loss. Results Hair problems were reported in 307 (61.4%) of COVID-19-infected female subjects. A total of 68.1% patients reported that hair loss existed and increased after COVID-19; 29.6% reported their hair problems only post-COVID-19 while 2.3% had hair shedding issues during infection only. The main reported hair problems were telogen effluvium (60.8%), increased gray hair (13.8%), seborrheic dermatitis (5.6%) trichotillomania (3.6%), and alopecia areata (2.2%). Conclusion In conclusion, we reported prevalence of post-COVID hair fall that was confirmed by trichoscopy and which affected approximately 61.4% of infected females.


Background
The coronavirus disease 2019 (COVID-19) has become the most emergent health issue globally.SARS-CoV-2, the pathogen of COVID-19, directly infects multiple tissues and organs, possibly involving skin and hair follicles, and profoundly affects the immune system [1,2].
Telogen effluvium (TE) and hair loss following bacterial, viral, or protozoal infection had been earlier reported and was of major concern during the 1918 influenza epidemic [3].Literature review in terms of the impact of COVID-19 infection on the hair follicle reveals hair loss caused during and post-recovery, majorly manifesting as TE [1][2][3].
The virus may infect the hair follicles directly or indirectly through systemic changes in the immune or hormonal systems [4].Furthermore, it is plausible to believe that alopecia may influence or predict the severity and course of COVID-19.A growing number of reports have focused on the clinical manifestations and pathophysiology of COVID-19-associated hair diseases [4,5].
In the current study we aimed to determine the prevalence of hair disorders in females infected with COVID-19.For that we enrolled 500 female patients post-COVID-19 and they were asked questions about pre-and post-pandemic hair diseases.All patients were subjected to online questionnaire containing 25 questions which have been divided into four domains (personal data, medical past history, diagnoses and treatment of COVID-19 infections, hair problems and their management).

Methods
This was a multi-center, cross-sectional study conducted from January 2022 to January of 2023.A total of 500 female participants attending dermatology clinics at university as well as ministry of health hospitals were included in the study after their consenting.The study followed the Helsinki declaration principals.Ethical approval was obtained from the institutional review board of Damietta Faculty of Medicine (Al-Azhar University).Written informed consent was obtained from every patient at recruitment.Inclusions included females aged 18-55 years of age whom were diagnosed with COVID-19 infection confirmed by using the reverse transcription polymerase chain reaction (RT-PCR) test of pharyngeal and nasal swabs (only those who finished the management protocol and had been discharged at least 6 months prior to joining the study).Those who were aged less than 18 years or above 55 years were excluded.
Data was collected using a questionnaire covering four main domains: personal data, past medical history, COVID-19 history and treatment, and existence of any hair problems and their management.No identifier or sensitive data were collected.Those complaining of hair loss were subjected to complete general and local hair examination using trichoscopy to confirm hair loss.Dermoscopic evaluation (DermLite DL4) and imaging were reproduced and saved.
The study was conducted in accordance with the Declaration of Helsinki and upon approval by the Local Ethical Committee-Al Azhar University IRB (00012367-21-06-005). Statistical analysis using continuous variables were presented as mean ± SD (standard deviation) for parametric data and median (min-max) for non-parametric data.Qualitative data were described using number and percent.Association between categorical variables was tested using Chi-square test.For all statistical tests p-value > 0.05 was considered not-significant and p-value < 0.05 was considered significant.All data were analyzed using IBM SPSS Statistics for Windows, Version 26, and Microsoft Excel 365.
Hair problems were reported in 307 (61.4%) of COVID-19-infected female subjects.A total of 68.1% patients reported that hair loss existed and increased after COVID-19; 29.6% reported their hair problems only post-COVID-19, while 2.3% had hair shedding issues during infection only.The main reported hair problems were telogen effluvium (60.8%), increased gray hair (13.8%), seborrheic dermatitis (5.6%), trichotillomania (3.6%), and alopecia areata (2.2%).Hair loss occurred after 2-3 months of COVID-19 infection among 93 (18.6%) cases, while 213 (42.6%) patients noticed hair loss after 6 months of the infection.Of the participants with hair problems, 65.2% did not use any treatment; 8.2% of them used treatment based on past experiences; 7.6% received prescription medications through physician telemedicine calls; and only 10.4% visited a dermatologist (Figs. 1, 2, 3 and Table 3).The prevalence of hair loss was significantly higher among those in the 31-40-year age group when compared to other age groups (p < 0.001).In addition, hair loss was significantly higher among HCWs, divorced, and widow females (Table 4).The prevalence of post-infection hair loss was significantly higher among females complaining of a hypercoagulable state while a significantly less prevalence of hair loss was found among females with hypertension and those   complaining of a psychiatric condition (p < 0.01).Other factors were insignificantly associated with post-infection hair loss.More prevalent hair loss was reported among those who needed hospital and ICU admission as well as among those complaining of severe respiratory symptoms and shortness of breath (p = 0.001, p = 0.002, respectively).Of notice hair loss was significantly higher among those who used antibiotics for COVID treatment (p = 0.027) (Tables 5, 6 and 7) .

Discussion
The current study was conducted to assess the prevalence of hair loss after COVID-19 infection and the factors associated with post-COVID-19 hair loss among 500 female study Results in the current study were in accordance with a major Saudi study that assessed the prevalence of hair loss following COVID-19 infection as well as the factors associated with post-COVID-19 which revealed that nearly half of their participants (48.5%) noticed an increase in hair loss of more than 120 hairs per day after COVID-19 infection, and half of the participants (52.6%) reported hair accumulation on a pillow [6].Another study recruiting a total of 806 participants reported that 52.7% experienced hair loss after COVID-19 infection.Age, gender, high temperature during, and the presence of hair loss prior to infection were significantly associated with the incidence of telogen effluvium (TE) [7].According to a study conducted in Brazil via remote SMS messages and electronic form fill ups by patients of COVID-19 saved on the national registry, hair loss was the most frequently reported post-COVID-19 manifestation in 2800 subjects that comprised 48% of the studied cohort [8].
TE is a type of reactive non-scarring hair loss that causes hair shedding and is more common in women.TE is a harmless disorder that has been linked to hormonal changes, extreme dieting, infections, and the use of anticoagulant medications, prescribed for treating COVID-19 patients [13].
In the current study, there was higher significance of hair loss among users of vitamins, expectorants, and antitussive medications (p < 0.05) while a non-significant prevalence of hair loss was encountered among users of anticoagulants (p = 0.173).Of notice hair loss was significantly higher among those who used antibiotics for COVID treatment (p = 0.027).Some medications used to treat COVID infection were reported to trigger telogen effluvium (enoxaparin, hydroxychloroquine, azithromycin, etc.).On the other hand, there is currently conflicting evidence regarding their mechanisms.Regarding the prophylactic anticoagulant therapy used in patients affected by SARS-CoV-2, most studies reported important associations of hair loss in these patients, possibly due to collagen degeneration of the follicular sheath [14].
The COVID-19 pandemic has increased the levels of anxiety and stress-related disorders among individuals which contributed to hair shedding and TE.Rates of acute hair shedding during the pandemic increased for which patients requested treatments to break such cycle.Interestingly, we found that only 25.2% of patients sought medical advice through phone calls and visit to general physician or dermatologists, similar to the rate of 18.9% reported by Turkmen et al. [11] and 22.9% reported by Alsalhi et al. [15].
In the current report, more prevalent hair loss was reported among those who needed hospital and ICU admission as well as among those complaining of severe respiratory symptoms and shortness of breath (p = 0.001, p = 0.002, respectively).Regarding the severity of the infectious episode, different studies revealed a positive correlation of hair loss and severity of infection requiring hospital or ICU admission and related this to increase in proinflammatory cytokines [14].
In specialized studies, smoking was frequently associated with the appearance of TE, due to influencing follicular apoptosis due to altering the sensitivity of acetyl choline receptor [10].In our case smoking did not appear to affect hair loss.The relationship between smoking and COVID-19 seems to be very controversial while smokers are susceptible to COVID-19; some reports suggested that it may also have a protective effect on the respiratory tract [16,17].
A number of mechanisms had been proposed for post-COVID hair loss involving direct endothelial cell damage; in addition, aggravation of existing hair loss was related to SARS-CoV-2 virus acting on the transmembrane serine protease 2 genes (TMPRSS2)-which has a role in the regulation of androgen pathways [4].Another cause of hair loss related the severity of the viral inflammation and cytokine storm to hair matrix cell destruction [5].Moreover, perifollicular inflammation manifested by the accumulation of activated macrophages and mast cell degranulation in the context of psychological stress as well as the ischemia and vascular decompensation caused by the hypercoagulability state and microthrombus formation were described as major culprits in inducing hair loss [18].Moreover, a recent study reported an increased incidence of hair shedding following COVID-19 vaccinations [19].
The following study is limited by its cross-sectional nature and by its gender bias on a female population in a localized community.Objective measures such as inflammatory biomarkers and oxygen saturation which are detrimental for the severity of infection have not been measured.Moreover, a lack of scalp biopsy remains to be a limitation.

Conclusion
In conclusion, we reported prevalence of post-COVID hair fall that was confirmed by trichoscopy and which affected approximately 61.4% of infected females.Other factors, such as stress and infection, cannot be excluded and remain to be further investigated by larger multicenter studies.

Fig. 1 A
Fig. 1 A Clinical image of a 32-year-old female showing reduced hair density with widened hair over the vertex and mid-frontal scalp.B Dermoscopy image showing great variability in the thickness of hair shaft or hair shaft diversity, vellus hair (red arrow), and peripilar sign (orange arrow) suggestive of androgenetic alopecia

Fig. 2 AFig. 3 A
Fig. 2 A Clinical image showing localized shedding of hair in the frontal area of the scalp surrounded by preserved hairs in a 22-yearold female.B Dermoscopy image showing yellow dots (orange arrow), black dots (green arrow), broken hair (red arrow), and tapering hair (black arrow) suggestive of alopecia areata.C Clinical image of a 21-year-old female showing reduced hair density all over the scalp with gray hair appear recently (red arrows).D Dermoscopy image showing upright re-growing hair (blue arrow), single hair emerging from the hair follicles (red arrows), and no hair shaft diversity suggestive of telogen effluvium

Table 1
Sociodemographic characteristics of the studied cases

Table 5
Comparison of associated comorbidities among studied cases

Table 3
Hair loss data among studied cases