Baricitinib as a novel treatment for bullous pemphigoid: a case series report (preprint)

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly. The standard treatment of BP patients with systemic corticosteroid have some potential serious side effects. Up till now, there is still lack of novel treatment for BP patients. Baricitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor, has been used to treat rheumatoid arthritis, alopecia areata, and COVID-19. Successful treatment of refractory BP by JAK inhibitors has been reported in sporadic cases. In this study, we reported 8 BP patients treated with baricitinib. The patients after treatment were followed up for 3-24 months, with an average of 9.1 months. All 8 cases achieved disease control and the mean disease control period was 3 weeks (1-6 weeks). The bullous pemphigoid disease area index total (21.2 ± 13.0 to 2.5 ± 4.3, p<0.01), erosion/blister (6.0 ± 7.7 to 0.2 ± 0.5, p<0.05), urticaria/erythema (10.2 ± 11.9 to 0.0 ± 0.0, p=0.06), mucosal erosion/blister (10.0 ± 6.4 to 4.5 ± 5.1, n=4, p=0.25) and itching NRS (3.6 ± 3.5 to 0.0 ± 0.0, p=0.06) scores were all reduced after 2 months’ treatment. Seven of 8 patients achieved complete remission during tapering at month 3 and did not experience relapse during the follow-up period. The serum levels of anti-BP180 autoantibodies (IgG) were reduced significantly (77.1 ± 47.8U/mL to 40.1 ± 37.1U/mL, n=6, p<0.05) after 3 months’ treatment. During the follow-up period, only one patient experienced mild elevation of serum creatinine level after 3 months’ treatment of baricitinib, which returned to normal through discontinuation of the medication. In conclusion, this study demonstrated that low-dose, short-term administration of baricitinib is effective and safe for treating BP patients.

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review.

BACKGROUND AND OBJECTIVES: Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several safety data for JAK inhibitors are extrapolated from a single study in elderly patients with rheumatoid arthritis treated with tofacitinib or adalimumab/etanercept as a comparator. The population of patients with alopecia areata is clinically and immunologically different from persons with rheumatoid arthritis and tumor necrosis factor (TNF) inhibitors are not effective in these patients. The objective of this systematic review was to analyze available data on the safety of various JAK inhibitors in patients with alopecia areata. METHODS: The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was performed by searching PubMed, Scopus and EBSCO databases with the last search on March 13, 2023. RESULTS: In total, 36 studies were included. The frequency and odds ratio (OR) for most common adverse events versus placebo were: for baricitinib hypercholesterolemia (18.2% vs 10.5%, OR = 1.9) and headache (6.1% vs 5.1%, OR = 1.2), for brepocitinib elevated creatinine level (27.7% vs 4.3%, OR = 8.6) and acne (10.6% vs 4.3%, OR = 2.7), for ritlecitinib acne (10.4% vs 4.3%, OR = 2.6) and headache (12.5% vs 10.6%, OR = 1.2) and for deuruxolitinib headache (21.4% vs 9.1%, OR = 2.7) and acne (13.6% vs 4.5%, OR = 3.3). The respective numbers for upper respiratory infections were: baricitinib (7.3% vs 7.0%, OR = 1.0) and brepocitinib (23.4% vs 10.6%, OR = 2.6); for nasopharyngitis: ritlecitinib (12.5% vs 12.8%, OR = 1.0) and deuruxolitinib (14.6% vs 2.3%, OR = 7.3). CONCLUSIONS: The most common side effects of JAK inhibitors in patients with alopecia areata were headache and acne. The OR for upper respiratory tract infections varied from over 7-fold increased to comparable to placebo. The risk of serious adverse events was not increased.

Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials.

BACKGROUND: Baricitinib, an oral, selective, reversible Janus kinase (JAK)1/JAK2 inhibitor, is an approved treatment for adults with severe alopecia areata (AA) in the USA, European Union and Japan. OBJECTIVES: To report safety data for baricitinib in patients with severe AA from two clinical trials including long-term extension periods. METHODS: This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE-AA2) (ClinicalTrials.gov, NCT03570749 and NCT03899259). Data are reported in three datasets: (i) the placebo-controlled dataset (up to week 36): baricitinib 2 mg and 4 mg vs. placebo; (ii) the extended dataset (up to the data cutoff): patients remaining on continuous treatment with baricitinib 2 mg or 4 mg from baseline; and (iii) the all-baricitinib dataset (all-BARI, up to the data cutoff): all patients receiving any dose of baricitinib at any time during the trials. Safety outcomes include treatment-emergent adverse events (TEAEs), adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates (IR) were calculated. RESULTS: Data were collected for 1303 patients who were given baricitinib, reflecting 1868 patient-years of exposure (median 532 days). The most frequently reported TEAEs during the placebo-controlled period (based on the baricitinib 4-mg group) were upper respiratory tract infection, nasopharyngitis, headache, acne and elevated blood creatine phosphokinase (CPK). During the placebo-controlled period, the frequency of acne was higher with baricitinib than placebo, and elevated CPK was higher with baricitinib 4 mg than placebo and baricitinib 2 mg. In all-BARI, the IR of serious infections was low (n = 16, IR 0.8). There was one opportunistic infection (IR 0.1), and 34 cases of herpes zoster (IR 1.8). There was one positively adjudicated major adverse cardiovascular event (myocardial infarction) (IR 0.1), one pulmonary embolism (IR 0.1), three malignancies other than nonmelanoma skin cancer (IR 0.2) and one gastrointestinal perforation (IR 0.1). No deaths were reported. CONCLUSIONS: This integrated safety analysis in patients with severe AA is consistent with the overall safety profile of baricitinib. Some differences with atopic dermatitis were noted that may be attributable to the disease characteristics of AA.

Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

BACKGROUND: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. METHODS: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807. FINDINGS: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. INTERPRETATION: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. FUNDING: Pfizer.

Efficacy and Safety of Baricitinib in Patients with Severe Alopecia Areata over 52 Weeks of Continuous Therapy in Two Phase III Trials (BRAVE-AA1 and BRAVE-AA2).

BACKGROUND: The oral Janus kinase (JAK) inhibitor baricitinib has demonstrated efficacy for severe alopecia areata (AA) over 36 weeks. There are limited data on the longer-term treatment of AA. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of baricitinib for AA in adults with ≥50% scalp hair loss through 52 weeks of continuous therapy in two phase III trials (BRAVE-AA1 and BRAVE-AA2). METHODS: Patients randomized to baricitinib at baseline in BRAVE-AA1 (N = 465) and BRAVE-AA2 (N = 390) retained their treatment allocation through Week 52. Efficacy outcomes included the proportion of patients achieving a Severity of Alopecia Tool (SALT) score ≤ 20 (≤ 20% scalp hair loss). Data were censored after permanent treatment discontinuation or if collected remotely due to the coronavirus disease 2019 (COVID-19) pandemic. RESULTS: Response rates for hair regrowth increased over the 52-week period. Of patients treated with baricitinib 4 mg and 2 mg, respectively, 40.9% and 21.2% in BRAVE-AA1 and 36.8% and 24.4% in BRAVE-AA2 achieved a SALT score ≤ 20 at Week 52. The most frequent treatment-emergent adverse events included upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection, creatine phosphokinase elevation, and COVID-19 infection. LIMITATION: There were no comparisons with placebo. CONCLUSION: Efficacy of baricitinib for adults with severe AA continuously improved over 52 weeks, indicating that long-term treatment may be necessary to observe maximum clinical benefit. There were no new safety signals. CLINICALTRIALS REGISTRATION: ClinicalTrials.gov NCT03570749 and NCT03899259. Efficacy and Safety of Baricitinib in Patients with Severe Alopecia Areata: Week-52 Results from BRAVE-AA1 and BRAVE-AA2.

Alopecia areata (AA) is an autoimmune disease that causes patchy hair loss on the scalp, face, and body. Baricitinib is a Janus kinase inhibitor that is approved to treat AA in several countries, based on results from two studies, BRAVE-AA1 and BRAVE-AA2. In these studies, adults with at least 50% scalp hair loss were treated with baricitinib for 36 weeks. Long-term therapy is important in AA, and hair regrowth can take longer in some patients with severe disease. Therefore, we assessed outcomes from a longer course of therapy. In this study, we report the results after 52 weeks of continuous treatment with baricitinib 4 mg or 2 mg in 465 patients in BRAVE-AA1 and 390 patients BRAVE-AA2. The goal was to reduce scalp hair loss to 20% or less by Week 52. In BRAVE-AA1, 40.9% of patients who took baricitinib 4 mg and 21.2% of patients who took baricitinib 2 mg had 20% or less missing scalp hair by Week 52. Similarly, in BRAVE-AA2, 36.8% of patients who took baricitinib 4 mg and 24.4% of patients who took baricitinib 2 mg had 20% or less missing scalp hair by Week 52. The most common adverse effects that were reported during the study period were upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection, creatine phosphokinase elevation, and coronavirus disease 2019 (COVID-19) infection. The results of longer-term treatment indicate that hair regrowth continues to improve without any new safety concerns for adults with severe AA taking baricitinib.

Reversal of Stress-Associated Alopecia.

Novel coronavirus SARS-CoV-2, designated as COVID-19 by the World Health Organization (WHO) on February 11, 2020, is one of the highly pathogenic β-coronaviruses that infects humans.1 Alopecia areata (AA) is a chronic inflammatory disease with sudden hair loss.2,3 There is strong evidence that AA is a tissue-specific autoimmune disease that develops based on genetic predisposition.4 In several patients, acute or chronic psycho-emotional stress may be causing the initiation and/or progress of AA.5 It is suggested that psychological stress can trigger or exacerbate inflammatory skin diseases through the neuroendocrine system, which is an essential connection between the brain and the skin.6,7 Hair loss has emerged as a frequently noted side effect of infection with COVID-19, and has been observed in many patients who have recovered from a documented COVID-19 illness.8,9.

Post-COVID Telogen Effluvium.

Recently, the number of patients with acute telogen effluvium (ATE), among other forms of hair loss, has increased in comparison with previous years. The COVID-19 pandemic, taking place during this period, may be the cause of this phenomenon. The exact mechanisms by which this virus causes hair loss are not entirely understood; still, the most likely cause is an excessive release of proinflammatory cytokines during SARS-CoV-2 infection. This process can trigger the development of telogen effluvium (TE) by damaging hair matrix cells. Additionally, the psychosocial condition of patients recovering from COVID-19 will have deteriorated, contributing to hair loss. Based on data collected until now, post-COVID TE is expected to improve without any treatment. Although there is no specific treatment for post-COVID TE, eliminating psychophysical stress, managing systemic complications, and explaining the course of the condition to the patient will potentially improve and speed up the hair recovery process.

COVID-19 infection is a major cause of acute telogen effluvium.

BACKGROUND: Acute telogen effluvium is a non-scaring hair loss, usually occurs 3 months after the stressful event that causes hair shedding, and lasts up to 6 months. It can be associated with post COVID-19 infection. OBJECTIVE: To study the possible effects of COVID-19 on the hair growth cycle and the relationship between COVID-19 and acute telogen effluvium. PATIENTS AND METHODS: This is an observational cross-sectional study that had been conducted during the period from September 2020 to March 2021 years. Thirty-nine patients with post COVID-19 hair loss are confirmed by polymerase chain reaction (PCR) or antibody testing. Hair pull test was carried out to confirm the diagnosis and severity of telogen effluvium. RESULTS: Thirty-nine patients were evaluated; their ages ranged from 22 to 67 years with a mean and SD of 41.3 ± 11.6 years with 36 (92.3%) females and 3 (7.69%) males. All patients with a diagnosis of ATE were enrolled in this study and had a laboratory-confirmed diagnosis of prior SARS-CoV-2 infection; 15 (38.46%) patients reported mild symptoms, 24 (61.53%) patients presented with moderate disease, and no patient required hospitalization. They all experienced excessive hair loss within 2-3 months after infection. Pull tests were strongly positive (> 10-50% with a mean of 35% of pulled hair away from scalp). CONCLUSION: COVID-19 infection is now a frequent and a common cause of acute telogen effluvium. Hence, clinicians should be aware about the relation between this infection and this pattern of hair loss. Drugs that have been used for the treatment of COVID-19 were excluded as a cause of acute telogen effluvium.

SYMPTOMATOLOGY AND TREATMENT OF COVID-19 AFFECTING SKIN APPENDAGES: A NARRATIVE REVIEW BEYOND COVID-TOES.

SARS-CoV-2 is the cause of COVID-19 disease and responsible for a pandemic since the 2020. Multiple organ involvement has been described including cutaneous symptoms. Affection of skin appendages, however, seems to be under-reported except for COVID-toes. We performed a PUBMED research for "COVID-19" OR "SARS-CoV-2" AND "skin appendages", "hair", "nails", and "skin glands" from January 2020 to April 2022. COVID toes were excluded since this symptom had extensively been discussed. The focus of this narrative review was laid on clinical presentation, association to the course of COVID-19 disease and treatment options. Skin appendages can be affected by COVID-19 disease beyond COVID-toes, both by symptomatic and asymptomatic course. Telogen effluvium, androgenetic alopecia, and alopecia areata are the most common hair disorders in COVID-19 patients. Nails are less commonly affected by COVID-19 than hair. Splinter hemorrhages and leukonychia are the most frequent findings. While sebaceous glands seem to be uninvolved, SARS-CoV-2 spike proteins have been identified in eccrine sweat glands. Alopecia areata is often seen among asymptomatic COVID-19 patients while telogen effluvium is observed in symptomatic and asymptomatic patients. The half-moon sign on the nails could be a red flag for a more severe course of COVID-19. Treatment options are summarized. Skin appendages are not spared by COVID-19. Their knowledge will help to identify asymptomatic patients and patients at risk for a more severe course of the viral disease.

Cutaneous manifestations of COVID-19 and COVID-19 vaccination.

In December 2019, a new infectious pathogen named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. Transmitted through respiratory droplets, SARS-CoV-2 is the causative pathogen of coronavirus disease 2019 (COVID-19). Although this new COVID-19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. These manifestations with COVID-19 can be classified into seven categories: (i) chilblain-like skin eruption (e.g., COVID toes), (ii) urticaria-like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster. The pathogenesis of skin eruptions can be broadly divided into vasculitic and inflammatory skin eruptions. Various cutaneous adverse reactions have also been observed after COVID-19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune-mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain-like lesions and herpes zoster after COVID-19 mRNA vaccination have been published. Various skin diseases associated with COVID-19 and COVID-19 vaccination have been reported, and the mechanism has been partly elucidated. In the process, for example, some papers have reported that it is not related to COVID-19 infection, although it was initially called COVID-toe and considered a COVID-19-associated cutaneous eruption. In fact, some COVID-19-associated skin reactions are indistinguishable from drug eruptions. In the future, the mechanisms of COVID-19- or COVID-19 vaccine-associated skin reactions need to be elucidated and verification of causal relationships is required.

Hair Loss and Telogen Effluvium Related to COVID-19: The Potential Implication of Adipose-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma as Regenerative Strategies.

The diffusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inducing coronavirus disease 2019 (COVID-19) has increased the incidence of several dermatological disorders, including hair loss (HL). This article aims to review the literature regarding the incidence of HL and telogen effluvium (TE) in COVID-19 patients and critically appraise the available evidence regarding the role of regenerative strategies like Platelet-Rich Plasma (PRP) and Human Follicle Stem Cells (HFSCs). A literature review regarding the correlation of HL and TE in COVID-19 patients analyzing the biomolecular pathway involved and the role of regenerative strategies was performed using PubMed, MEDLINE, Embase, PreMEDLINE, Scopus, and the Cochrane databases. Observational studies revealed an escalated incidence of pattern HL and TE in COVID-19 patients. Psychological stress, systemic inflammation, and oxidative stress are potential culprits. Proinflammatory cytokines and stress hormones negatively affect the normal metabolism of proteoglycans. Reduced anagenic expression of proteoglycans is a potential mediating mechanism that connects HL to COVID-19. Currently, only one study has been published on PRP against HL in COVID-19 patients. Further controlled trials are required to confirm PRP and HFSCs efficacy in COVID-19 patients.

Simple prediction of COVID-19 convalescent plasma with high levels of neutralization antibodies (preprint)

Background: Hyperimmune convalescent COVID-19 plasma (CCP) containing anti-SARS-CoV-2 neutralizing antibodies (NAbs) was proposed as a therapeutic option for patients early in the new coronavirus disease pandemic. The efficacy of this therapy depends on the quantity of neutralizing antibodies (NAbs) in the CCP units, with titers > 1:160 being recommended. The standard neutralizing tests (NTs) used for determining appropriate CCP donors are technically demanding and expensive and take several days. We explored whether they could be replaced by high-throughput serology tests and a set of available clinical data. Methods: Our study included 1302 CCP donors after PCR-confirmed COVID-19 infection. To predict donors with high NAb titers, we built four (4) multiple logistic regression models evaluating the relationships of demographic data, COVID-19 symptoms, results of various serological testing, the period between disease and donation, and COVID-19 vaccination status. Results: The analysis of the four models showed that the chemiluminescent microparticle assay (CMIA) for the quantitative determination of IgG Abs to the RBD of the S1 subunit of the SARS-CoV-2 spike protein was enough to predict the CCP units with a high NAb titer. CCP donors with the respective results >6000 AU/ml SARS-CoV-2 IgG had an 80% probability of attaining high NAb titers. Including additional variables such as donor demographics, clinical symptoms, or time of donation into a particular predictive model did not significantly increase its sensitivity and specificity. Conclusion: A simple quantitative serological determination of anti-SARS-CoV-2 antibodies alone is satisfactory for efficiently predicting CCP donors with high titer NAbs.

Tofacitinib in paediatric dermatoses: a narrative review.

Tofacitinib has revolutionized the treatment of numerous dermatological conditions in different age groups. However, evidence for its effectiveness, safety and tolerability in the paediatric population is limited. We performed a literature search, which showed that oral tofacitinib is a reliable option in refractory juvenile dermatomyositis, severe alopecia areata, atopic dermatitis and psoriasis. Topical tofacitinib is an effective option in vitiligo and halo naevus. The risk-benefit ratio should be assessed prior to consideration of this molecule. In this narrative review, we have attempted to present a summary of the evidence of using tofacitinib (oral and topical) in paediatric dermatoses.

Prevalence of telogen effluvium hair loss in COVID-19 patients and its relationship with disease severity.

COVID-19 is a concerning global pandemic. Common manifestations are fever and respiratory symptoms. In addition, recent studies reported dermatological manifestations as extrapulmonary signs. One of these is telogen effluvium which is related to post COVID-19 comorbidities. The aim of this study was to assess the prevalence of telogen effluvium among COVID-19 patients. This observational cross-sectional study included 198 patients who were admitted for COVID-19. The PCR test was performed to detect positive cases. After discharge, all patients were interviewed about hair loss. Of these patients, 79 were male (39.9%), and 119 were female (60.1%). The age ranged from 18 to 85 years old. 48 patients showed hair loss. Telogen effluvium (TE) is one of the consequences of the COVID-19 pandemic. COVID-19 leads to more medications and stress situations, which trigger TE.

Characteristics of hair loss after COVID-19: A systematic scoping review.

OBJECTIVE: While there are literature reporting increased incidence of hair loss in COVID-19 patients, insufficient evidence exists on the topic to date. This review aims to identify the existing evidence and clinical characteristics of hair loss with COVID-19 infection. METHODS: Following the PRISMA Extension for Scoping Reviews, MEDLINE and EMBASE were searched for all peer-reviewed articles with relevant keywords including "Alopecia," "Telogen Effluvium (TE)," and "COVID-19" from their inception to November 20, 2021. RESULTS: A total of 26 articles, with 9 observational studies and 17 case reports or series (a total of 58 cases), were included. Most studies dealt with TE. There were no clear trends between COVID-19 severity and the extent of hair loss. Analysis of the 58 cases also found similar results with most of the cases being female (82.8%), the median onset of hair loss of 2.0 months, and the median time to recovery of hair loss of 5.0 months with a resolution rate of 95%. CONCLUSION: While this systematic review revealed uncertainty and a lack of strong evidence regarding the association of COVID-19 and hair loss, hair loss in COVID-19 may mainly include TE and be reversible in nature. Future studies are warranted to determine the detailed pathophysiology and risk factors of hair loss in COVID-19, including possible roles of estrogen, progesterone, and pro-inflammatory cytokines.