COVID-19 infection was a cause of global pandemic and there has been extensive research to guide diagnosis, management and prevention of the same. However, post recovery symptoms have been equally harrowing, with survivors showing varied symptoms ranging from fatigue, dyspnoea, headache, attention deficit to hair loss. Post COVID-19 hair loss has been reported to be one of the five most common post recovery symptoms [12]. We conducted this study to assess the clinical, hematological, biochemical and trichoscopic features in patients with post COVID-19 hair loss due to sudden surge in patients presenting with the same.
The mean age of patients reported in our study (39.6 years) was similar to that reported by Sharquie et al (41.3 years). However, both younger (mean age 31 years) and older age groups (49 years) have been affected, which could possibly be due to geographical variation in the prevalence of COVID-19 infection [5,13,14]. There was a female preponderance in the present study, as seen in other studies as well, possible explanations being, longer hair length and higher vulnerability of female hair follicles due to role of estrogen and progesterone hormones in the pathophysiology of hair loss [1,2,5,11,14-17]. Higher prevalence of anemia (20%) and low ferritin levels (30%) in our patients who were predominantly females, can also be a contributing factor; as was also observed by Babaei et al who reported the presence of iron deficiency anemia in 13.8% of their patients [14].
The mean VAS score for stress in our study was 5.25, which was comparatively lower than that reported by Rivetti et al (8.2) [18]. Stress, however, has been noted to induce as well as increase the hair loss during and post COVID-19 pandemic [19]. We also found that the mean VAS score was significantly higher in patients who were hospitalized for COVID-19 infection and who had infection for more than 2 weeks, hence, correlating with the severity of infection. However, it was not significantly associated with the degree of hair loss in our study. The relationship between stress and hair cycle changes has given rise to the concept of “brain-hair follicle axis”, wherein the release of specific neuropeptides, neurotransmitters, and hormones along this axis may promote changes in the hair growth cycle by shifting the hair from anagen to telogen, promoting hair loss [18]. An unexpected finding was that 47.5% of study population had a family member with post COVID-19 hair loss, indicating its high prevalence and illustrating the importance of taking a good family history.
Pre COVID-19 hair loss was observed more frequently in our patients (37.5%) compared to a study by Abdulwahab et al (15.5%). The latter reported a greater number of cases of TE and alopecia areata vis-à-vis the present study. We, however, observed a higher proportion of patients with patterned hair loss [1]. Interestingly, majority of our cases with pre-existing hair loss had mild to moderate degree of hair loss post COVID-19 infection.
Current hair loss in our study was predominantly diffuse type, followed by patterned type with overlap of diffuse, patterned and/or alopecia areata in a few cases. In contrast, Abdulwahab et al reported greater number of cases of TE and alopecia areata and lesser number of cases with patterned hair loss [1]. Meanwhile, Babaei et al in their study on TE following COVID-19 infection in Iran, found androgenetic alopecia as the most common concomitant pattern with TE [14]. Another study on hair loss post COVID-19 infection reported majority cases of TE and only few cases of alopecia areata and fibrosing alopecia [11]. We noted a relatively higher percentage of patterned hair loss, possibly because of high prevalence of pre-existing patterned hair loss in our study population. Another possible explanation could be that COVID-19 infection exacerbated or triggered patterned hair loss [20].
The mean time of onset of hair loss post COVID-19 infection in our study was 49 days, which was comparable to that found in other studies (7-9 weeks) [5,11,14-16,21-24]. Starace et al observed earlier onset of hair loss in patients with trichodynia (3 weeks), however we observed no such difference [25]. The mean time of onset of hair loss post COVID-19 infection is earlier than the classic TE, possibly because of pathogenetic mechanisms implicated in post COVID-19 hair loss [5]. These include intense release of pro inflammatory cytokines including IL-6, IL-4, IL-10, matrix metalloproteinase (MMP) 1 and 3, which induce catagen, cause premature anagen release, have cytotoxic effects on keratinocytes, inhibit stem cells and decrease hair growth [5,8]. Moreover, anticoagulant proteins are decreased in COVID-19 infection, causing microthrombi formation which obstruct the hair follicle blood supply resulting in hair loss. Increased stress hormones, oxidative stress and hypoxia during COVID-19 infection are all potential culprits that increase the tendency for hair loss [8]. Furthermore, direct viral damage to hair follicle has also been hypothesized [5]. Co-existing anemia, deficiency of Vitamin D and Vitamin B12, increased TSH and high stress level may also contribute. A significant proportion of our study population (43.3%) had COVID-19 infection for > 2 weeks, causing more sustained inflammation, possibly resulting in earlier onset of hair loss. However, we noticed no significant difference in onset of hair loss post COVID-19 infection amongst patients with or without hospitalization or duration of COVID-19 infection (≤ or > 2 weeks). Babaei et al reported early onset of hair loss in patients with hypothyroidism, younger age group and females [14].
Trichodynia was present in 15.8% and scalp itch in 10.8% of our study subjects. On the other hand, Starace et al observed trichodynia in 58.4% and trichodynia with TE in 42.4% of patients. They also found an association of trichodynia with dysgeusia and anosmia, postulating an underlying neurogenic pathogenesis for all [25]. Trichodynia corresponds to a complex symptom comprising scalp pain, pruritus or burning sensation on touching or combing through the scalp, which may be a sign of severity or a warning symptom of imminent hair shedding before hair loss begins [17,25].
Females showed a greater degree of hair loss compared to males, 61.2% of females vs 23.5% of males, difference being statistically significant. Older study subjects had more severe hair loss as has been previously reported in another study [14]. Degree of hair loss also correlated with duration of COVID-19 infection in our study, as majority of patients with COVID-19 infection for >2 weeks had severe hair loss. This can be possibly explained by sustained inflammatory or viral damage. Hospitalization, however, did not have any impact on the degree of hair loss in our study. The effect of hospitalization or COVID-19 severity on hair loss has been controversial so far. Even though studies have found that more than a fourth of the patients with acute TE post recovery were hospitalized during COVID-19 infection, others have reported that approximately 1 in 10 patients had subclinical infection or majority had only mild infection. [11,16,21]. Therefore, it is imperative that clinicians enquire about a history of preceding COVID-19 infection in last 1-3 months in all patients presenting with sudden hair loss in the context of the pandemic [21,24].
Trichoscopic evaluation is essential in all patients presenting with hair loss as it helps to uncover and guide towards clinically indistinguishable causes, like, differentiating diffuse alopecia areata from TE and patterned hair loss in early stages [26]. Even though, acute TE does not have any specific findings on trichoscopy, the most common features described are: decreased density of hair, empty hair follicles, numerous short regrowing hair of normal thickness and single hair follicles [5,17,21,22,24,27-31]. The commonest presenting complaint in our study was decreased hair density (in 90.8% of patients), which on trichoscopy was seen as increased interfollicular distance in 41.2% of study subjects. Empty hair follicle, another common trichoscopic finding in TE (which may also be seen in patterned hair loss), was observed in 50.8% of our cases. Also, single hair follicle, which has been previously reported in TE and patterned hair loss was seen in 43.3% of our patients [28,32]. Similar findings on trichoscopy have been described in case reports and small case series [5,15,22,31,33-35].
Anisotrichosis or hair diameter variability of 20% favours patterned hair loss over TE. Even though only 31.7% of study subjects clinically had patterned hair loss, anisotrichosis on trichoscopy was seen in 43.3% of patients, predicting that a significant proportion may eventually develop patterned hair loss in addition to diffuse hair loss [27,28]. In contrast to our finding, a few case reports have reported the absence of anisotrichosis [23,33,34,36].
An interesting finding in our study was the presence of vellus hair in 60% of patients, even though clinically majority had diffuse hair loss suggestive of TE. Similarly, vellus hair in fronto temporal region have been reported in a single case of TE post COVID-19 infection [31]. On the contrary, some studies observed absence of miniaturized hair in post COVID-19 TE [22,23]. As vellus hair are classically seen in patterned hair loss and alopecia areata, our study patients with vellus hair could represent overlap of TE with patterned hair loss or alopecia areata [28,29,32].
Yellow dots, which are a feature of alopecia areata and patterned hair loss, was seen in only 12.5% and perifollicular pigment, which has been reported in patterned hair loss, was seen in 14.2% of study subjects [28-30,32]. Even though clinically, scalp seborrhea and erythema were present in only 9.2% of cases; perifollicular scaling on trichoscopy was seen in 27.5% of cases. It has been speculated by previous studies that COVID-19 infection can exacerbate or precipitate flares of seborrheic dermatitis [37]. Lv et al also reported scalp inflammation, capillary ectasia and seborrhea on trichoscopy [36].
Another interesting finding in the present study was that patients who were hospitalized for COVID-19 infection had significantly greater number of empty hair follicles and vellus hair. These findings are suggestive that severe COVID-19 infection led to higher release of pro-inflammatory cytokines, thereby resulting in a significant increase in diffuse and possibly patterned hair loss. Association between hospitalisation for COVID-19 infection and patterned hair loss has been hypothesised in previous studies, which suggested androgen mediated SARS-CoV-2 vulnerability, and gave the eponym of Gabrin sign to visually identify people at an increased risk of hospitalization and negative outcomes. The Gabrin sign suggests that patients with higher degree of male pattern baldness are at higher risk of developing severe COVID-19 symptoms and requiring hospitalisation [7,8]. This has, however, been argued against, and it has been suggested by few studies and genetic association analysis, that patterned baldness in both women and men is not related to COVID-19 severity [4,9,10].
Hair loss has been a significant complaint in the post-acute COVID-19 syndrome, both in the subacute and chronic phase. The underlying cause has been documented to be TE (anagen effluvium as well as chronic TE), precipitation and exacerbation of alopecia areata, or patterned hair loss [1,3,38]. Our findings also suggest the same, with 67% of patients presenting in the subacute phase and 13% in the chronic phase, reiterating the need of awareness and vigilance in both patients and dermatologists alike.
The limitations of our study included the study population being limited to the patients specifically seeking dermatologist consultation at a tertiary care hospital and therefore, not representative of the general population. In addition, there was a lack of control group of patients with COVID-19 infection who did not suffer from hair loss. Histopathological confirmation of diagnosis was not carried out for underlying disorders, which may have led to over or underdiagnosis of a particular type of hair loss.
The present study elucidates the clinical, biochemical and trichoscopic features in patients presenting with post COVID-19 hair loss. Given the severe stress and anxiety that hair loss can have, along with potential long-term sequelae of diffuse and patterned hair loss, dermatologists need to be aware of this distressing effect of COVID-19 infection. Future areas of research include histopathological examination of hair follicles, genetic studies for susceptibility to hair loss and studies evaluating the roles of hormones (estrogen, progesterone and androgens) and inflammatory cytokines on the extent and duration of hair loss.