Telogen Effluvium in Patients Recovering from COVID-19

Telogen Effluvium (TE) is a non-scarring alopecia characterized by diffuse hair shedding that has recently been reported as a post-infectious manifestation of the novel coronavirus SARS-CoV-2. In response to physiological or psychological stress, premature termination of the anagen phase and subsequent transition to the telogen phase of hair growth result in shedding of hair follicles 2-3 months after the precipitating event. The condition is usually self-limited, with acute cases resolving within 6 months of onset. It has been proposed that proinflammatory cytokines, impaired anti-coagulation and severe psychosocial stress of COVID-19 triggers TE in survivors recovering from the disease. We describe ten cases of a telogen effluvium following COVID-19 infection from an ambulatory dermatology clinic in New York City, an early epicenter of the pandemic and review the current literature. ABSTRACT


1
The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY Telogen Effluvium (TE) is a non-scarring alopecia characterized by diffuse hair shedding that has recently been reported as a post-infectious manifestation of the novel coronavirus SARS-CoV-2. 1 In response to physiological or psychological stress, premature termination of the anagen phase and subsequent transition to the telogen phase of hair growth result in shedding of hair follicles 2-3 months after the precipitating event. The condition is usually self-limited, with acute cases resolving within 6 months of onset. 2 It has been proposed that proinflammatory cytokines, impaired anti-coagulation and severe psychosocial stress of COVID-19 triggers TE in survivors recovering from the disease. 3 We describe ten cases of a telogen effluvium following COVID-19 infection from an ambulatory dermatology clinic in New York City, an early epicenter of the pandemic and review the current literature.

INTRODUCTION
For the literature review portion , a PubMed search was conducted with the following terms, "telogen effluvium", "covid" and "hair" without any Boolean operators and investigation was limited to adult case reports and cohort studies appearing in the English-Language literature as of March 2021. Articles wherein the full text was not available or of an irrelevant publication type such as literature reviews, conference abstracts, posters, and editorials were excluded. Out of the eleven results, three did not match the publication type and three were not descriptive case reports. In total, five publications with reported cases of post COVID-19 TE were included in the study.
We report 10 patients who developed acute, new onset TE weeks after COVID-19 infection. Patient demographics and clinical features are summarized in Table 1. The patients ranged from 20 to 68 years old with a median age of 56 years and were 60% female. All patients had PCR or antibody confirmed COVID-19 infection and denied previous history of hair loss. No new medical conditions, medications, or lifestyle modifications aside from COVID-19 were reported. Only one patient was hospitalized for a severe COVID-19 infection that lasted 40 days and required 21 days of mechanical ventilation. The other nine patients exhibited mild symptoms limited to anosmia, congestion, cough, fatigue, fever, headache, lethargy, myalgias, nausea, progressive weakness, and shortness of breath that were treated in an outpatient setting. The mean duration of COVID-19 symptoms in these 9 patients was 9.89 days. The most common treatment for COVID-19 infection was acetaminophen (60%) followed by azithromycin (40%) and hydroxychloroquine (20%).
Overall, the average onset of hair shedding was 73 days after initial COVID-19 symptoms. The most common pattern of hair loss was diffuse hair thinning (80%) followed by bitemporal recession and thinning (50%). While over the counter minoxidil solution or foam was recommended to four of the patients, most did not receive any further treatment. At 14week follow-up, 50% of the patients' hair complaints had resolved.
A total of 28 patients with TE following laboratory confirmed COVID-19 infection were identified across five retrospective studies, case reports, and case series. Data analysis including patient demographics, medical intervention for COVID-19, duration of illness, time between COVID-19 infection and onset of hair loss, physical exam findings, treatment for telogen effluvium, and outcomes are summarized in Tables 2 and  3. Half of the patients who developed TE were hospitalized for treatment of severe COVID-19, while 35.7% of the patients experienced mild to moderate symptoms only. The average time between COVID-19 infection and onset of TE was 87 days with a standard deviation of 48 days. Most patients (82.1%) did not have any previous history of hair loss, while all others had a history of androgenic alopecia (AGA) or female pattern androgenic alopecia (FAGA).
The time between the stressor and onset of hair loss in Telogen Effluvium is equivalent to the length of the telogen phase, or approximately 3 months. 2,3 Consistent with this, the patients reported in  However, the majority of the TE patients described in this case series experienced mild COVID-19 symptoms.

DISCUSSION
Although hospitalizations and serious illness are known causes of telogen effluvium, mildto-moderate illness not requiring extensive medical intervention does not usually cause notable hair loss. Proteomic analysis comparing the serum of patients with active COVID-19 infections compared to healthy donors identified significant changes in inflammatory cytokines (e.g., CXCL6) and proteins associated with immune cell activation (e.g., CD244 and CD40) between the two groups. 8 In comparison, proteomic expression mild and severe COVID-19 patients do not demonstrate the same variability, implying high immune activation even in mildly symptomatic patients. As TE can be caused by a surge of inflammation, increased severity of COVID-19 infection does not necessarily correlate with increased risk for developing postinfectious TE. Literature on dengue fever associated TE similarly found no association between severity of infection and hair loss. 3,9 Additionally, coagulopathy studies of COVID-19 patients revealed coagulation functions remained fairly stable in mild COVID-19 and not significantly different from baseline (convalescent state) within the same individuals. 10 11 Patients with pre-existing TE have reportedly experienced worsened hair loss associated with the increased psychosocial stress induced by mandated quarantine. Psychological and emotional stressors are a known trigger for TE, so they may contribute to the new onset TE seen in COVID-19 patients. As our sample size is limited, we are unable to definitively determine a causal relationship between COVID infection and TE. Previous studies report that most cases of COVID-19-related TE occur in patients with severe infections, our investigation demonstrates that this phenomenon may also occur in mild to moderate cases of COVID-19. This is of particular relevance for dermatologists practicing in communities greatly affected by COVID-19, as they should expect to see a directly correlated increase in telogen effluvium cases in the months to follow. Patients should be educated on the increasing evidence of a causal link between TE and COVID-19 infection as well as reassurance regarding the self-limiting nature of the disease. The link between telogen effluvium and COVID-19 is still under evaluation, and further studies are needed to identify a causal relationship.