1 INTRODUCTION

Cutaneous manifestations such as chilblain-like acral eruptions, purpuric or erythema multiform-like lesions, acro-ischemic lesions, maculopapular rash, urticaria, and androgenetic alopecia (AGA) pattern hair loss were reported during COVID-19 disease.1 Androgenetic alopecia during COVID-19 based on a hypothesis that includes a common pathway with SARS-CoV-2 replication in human cells and transcription promoters for androgens.2 SARS-CoV-2 viral spike proteins undergo proteolytic priming by the transmembrane protease serine 2 (TMPRSS2) during entering the type II pneumocytes in the human. Androgens are the only known transcription promoters for the TMPRSS2 gene.3 In addition, milder disease severity in prepubertal children and adult women has been associated with a low androgen receptor transcription in the literature.3 Also, the correlation between AGA severity and COVID-19 severity has been observed earlier in the pandemic.4, 5 Rapidly progressive form of alopecia areata has been reported during COVID-19 infection.6 Accelerated hair loss with AGA pattern or management of this issue has not been discussed in the literature before.

2 PATIENTS AND METHODS

The study was designed prospectively between September 2020 and December 2020 at a second referral state hospital. All patients confirmed for COVID-19 infection with polymerase chain reaction (PCR). Patients with a history of any drugs, or systemic disease, or local dermatological disorder that may cause hair loss were excluded after a detailed anamnesis and physical examination. Laboratory tests including complete blood cell count, serum levels of iron and ferritin, folic acid, T3, T4, thyroid-stimulating hormone, testosterone, and Venereal Disease Research Laboratory blood test were performed to exclude other hair loss etiologies. Patients with new-onset accelerated hair loss with AGA were enrolled in the study. Patients who complained of hair loss admitted to hospital during six months following recovery from COVID-19 were also excluded.

Modified Norwood-Hamilton classification of the AGA was identified for all patients.7 Also, the hair pull test (HPT) was performed before each platelet-rich plasma (PRP) session. Informed written consent was then obtained after explaining the procedure. Patients underwent PRP injections per three weeks for four sessions. At the end of the treatment, patients assessed the result of treatment with a validated, self-administered hair growth questionnaire (HGQ).8 HGQ translated into the Turkish language by the authors. HGQ includes four questions about treatment efficacy and three questions on satisfaction with appearance.

About 20 ml of venous blood was drawn into a tube-containing anticoagulant sodium citrate. Blood was processed for the first centrifugation at 1500 rpm for 5 min, which separated blood into three layers (buffy coat). Using a sterile syringe, platelet-poor plasma (PPP) and PRP were transferred into another tube without an anticoagulant. This tube underwent second centrifugation, which performed at around 2500 rpm for 20 min. PPP was removed with a syringe and discarded, and the remaining PRP was collected into an insulin syringe. PRP was injected intradermally in a dose of 0.1–0.2 ml per injection approximately 1 cm apart in interfollicular areas on frontal areas and vertex, for a total of four sessions.

SPSS 22.0 program (IBM Corp., Armonk, NY, USA) was used for statistical analysis. The institutional review board was approved by the Provincial Health Directorate of Mardin for the study (Trial Number: 17_07_07/2021-02–11).

3 RESULTS

Nine patients were admitted with complaint of hair loss after an average of 220 ± 24.2 (min: 182, max: 264) day after recovery of COVID-19. Mean age of the patients was 33.8 ± 8.4 years old (min: 26, max: 52). Six (66.7%) patients were male and three (33.3%) of them were female. Four (44.4%) patient included Modified Norwood-Hamilton Scale type-1, three (33.3%) patients were in type-2 and two (22.2%) patient were type-3. The average hair was 10 ± 2.8 in the hair pull test performed from three different points of the scalp at the beginning of PRP treatment. Hair pull test score decreased to 6.0 ± 1.6 after the first PRP application (p = 0.007, CI 95%:2.7–5.2, Wilcoxon test). Hair pull test score decreased to 1.2 ± 0.8 after the last PRP session (p = 0.008, CI 95%: 6.4–11.1, Wilcoxon test). Hair pull test scores and comparisons between PRP sessions were shown in Figure 1. According to the hair growth questionnaire, seven (77.7%) of the patients described the increase in hair growth as “slightly” when the treatment was completed. Five (55.5%) of the patients described the treatment as “very effective” after treatment. The number of “very satisfied” patients after treatment was three (33.3%) and “satisfied” patients were 3 (33.3%), (Figures 2 and 3). The overall data were summarized in Table 1. The mean platelet count was detected as 214 × 103 platelets/µL (min: 174 × 103 max: 261 × 103 platelets/µL) in 36 prepared PRP. There were no local or systemic side effects or complications during or after the application.

Hair pull test scores before each PRP session and comparisons between sessions

34-year-old male patient, an image before (A) and after (B) treatment

31-year-old female patient, an image before (A) and after (B) treatment of left frontoparietal region

TABLE 1. Summary of the findings according to the Modified Norwood-Hamilton type of Androgenetic Alopecia Modified Norwood-Hamilton Scale 1, n = 4 2, n = 3 3, n = 2 Med Min Max Med Min Max Med Min Max Gender (n, %) Male 1 25 3 100 2 100 Female 3 75 0 0 0 0 Age 33 27 52 28 26 37 35 29 41 Duration After Diagnosis 217 207 238 202 182 213 253 241 264 Hair Pull Test at 1th Session 12 7 14 11 10 11 7 6 8 Hair Pull Test at 2nd Session 7 4 8 6 5 8 5 4 6 Hair Pull Test at 3th Session 3 2 3 2 2 4 4 2 6 Hair Pull Test at 4th Session 1 1 3 2 1 2 2 1 2 HGQ Q1 2 2 3 3 2 3 2 2 2 HGQ Q2 2 1 3 3 3 4 3 2 3 HGQ Q3 3 2 3 3 3 3 4 3 4 HGQ Q4 1 1 3 2 1 2 2 1 2 HGQ Q5a 2 1 3 2 2 3 2 2 2 HGQ Q5b 2 1 3 3 2 3 3 2 3 HGQ Q5c 2 1 3 2 2 2 2 1 3 Abbrevations: Med: Median, HGQ: Hair growth questionnaire, Q 1-5c: Questions 1-5c. 4 DISCUSSION

Platelet-rich plasma (PRP) injections for hair loss have been a very popular practice worldwide as a treatment modality, due to minimally invasive, cost-efficient, simple, and fast application.9 Because PRP consists of several growth factors, chemokines, and cytokines and may have possible promoting effect for tissue healing in hard and soft tissues such as cell survival and proliferation of the hair cycle, also tissue regeneration, bone regeneration, and wound repair.9, 10 A systematic review by Singh and Goldberg.11 discussed that PRP injections are the available treatment for different alopecia patterns with minimal side effects and complications. In this study, PRP treatment for accelerated hair loss in AGA pattern was presented in patients within the late-period of COVID-19 disease after recovery. At the end of the first session, a 25%–54% reduction in hair loss was achieved in all patients according to the hair pull test.

In a randomized placebo-controlled trial, significant clinical improvement in the mean number of hairs, with a mean increase of hairs in the target area and a mean increase in total hair density, compared with baseline values detected after two years follow-up with three PRP sessions.12 In a similar study, after 12 months with patients’ alopecia areata, PRP treatment significantly increased hair regrowth and decreased hair dystrophy compared with triamcinolone acetate or placebo.13

PRP contains highly concentrated growth factors which participate vary processes such as angiogenesis, cell proliferation, and differentiation. PRP treatment prolongs the hair follicle anagen phase and prevents premature catagen phase entry by promoting molecular cell growth mechanisms and preventing the onset of apoptotic processes.14 PRP injection also improves cutaneous ischemic conditions and increases vascular structures around hair follicles due to common mechanisms in the wound healing process.14, 15 Cervelli et al. showed a significant increase in the mean hair count, total hair density, and terminal hair density for the activated-PRP injection treatment in patients with male pattern hair loss compared with the control group at the third month of treatment.15 They also reported a significant increase in epidermis thickness with the number of follicles accompanied by an increase of Ki67+ in basal keratinocytes and hair follicular bulge cells. In addition, a proliferation of small blood vessels around hair follicles was observed in this study.15 In addition, growth factors and cytokine concentrations can be increased by collection systems to prepare activated PRP, thereby the clinical and histological benefits of this treatment may be enhanced.16 In this case series, we applied non-activated PRP injection prepared with sodium citrate due to the limitations of technical possibilities. We have seen a significant improvement in the increased hair loss of the patients, especially after the diagnosis of COVID-19. We also achieved a satisfactory rate in the survey after the treatment. However, the lack of histopathological evidence and the limited number of cases are the most important limitations of this case series.

Current drugs are available for the treatment of AGA such original molecules as finasteride and minoxidil. Also, other promising new strategies in hair regrowth based on the transfer of autologous cells were reported recently in several studies. The use of autologous micro-grafts facilitates the mechanical detachment of human hair follicle mesenchymal stem cells (HF-MSCs), human hair follicle epithelial stem cells (HF-ESCs), and adipose-derived mesenchymal stem cells (AD-MSCs).17-20 Low-level laser (light) therapy (LLLT) or laser phototherapy stimulates the proliferation of hair follicle and promotes anagen reentry in telogen hair follicles, prolongs the duration of the anagen phase, and prevents premature catagen development.21 Besides these autologous stem cell transfer technologies or laser treatments, PRP treatment can be applied easily and quickly with limited opportunities, especially during the COVID-19 pandemic.

Telogen effluvium is a nonscarring, diffuse, hair loss from the scalp that occurs within three months after a triggering event and is usually self-limiting, lasting for about 6 months.22 Recovery of COVID-19 disease was completed in all of nine patients included in this study at least six months ago and they had mild disease and none of them were hospitalized. None of the patients had complained of trichodynia when they noticed accelerated hair loss. In addition, 66.6% (n = 6) of the patients were male and alopecia in all patients was compatible with the AGA pattern, also Modified Norwood-Hamilton classification of patients was listed as type I-III. Nevertheless, although the pre-diagnosis of telogen effluvium seems more likely in these reported patients, it is difficult to distinguish it from AGA-related increased hair loss without histopathological findings. Especially in these patients recovering from COVID-19, both hair loss etiologies are likely to be found together. In this report, the absence of histopathological evidence and the low sample size are the most important limitations of the study.

5 CONCLUSION

COVID-19–associated skin lesions have been described in the literature, but there are very few articles on treatment and management yet. COVID-19—related hair loss is one of the remarkable issues and PRP injections with limited sessions may recommend for COVID-19—related hair loss.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

ETHICS APPROVAL

The institutional review board was approved by the Provincial Health Directorate of Mardin for the study (Trial Number: 17_07_07/2021-02–11).

DATA AVAILABILITY STATEMENT

All collected data were shared with the study. In addition, the data summary is shared here: https://drive.google.com/file/d/1_fBLkf0A2vbzSXXjVic_wTM07egnSJW4/view?usp=sharing.

CONSENT TO PARTICIPATE

Written consent was obtained from patients.

REFERENCES

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