Prevalence of Hair Loss After COVID-19 Infection in Makkah Region, Saudi Arabia

Introduction COVID-19, caused by SARS-CoV-2, is a worldwide pandemic with the most main symptoms seeming to be flu-like and fever. Besides that, dermatological manifestations have been reported as extra respiratory symptoms in previous studies. The aim of this study is to measure the prevalence of hair loss after COVID-19 infection in Saudi Arabia, and we hope to improve the knowledge on hair loss - a cause of common dermatological consultation that frequently becomes a stressful event associated with the pandemic - among all the physicians in all the specialties. Methodology This was a record-based retrospective cross-sectional, multicenter study conducted in four centers in the Makkah region. We identified 343 patients who visited the dermatology clinic for hair loss during the period 2020 to 2022. Results Evidence suggests that hair loss had been the most frequently reported post COVID-19 manifestation (48%). Our results revealed nearly half of the participants (48.5%) noticed hair loss increases by more than 120 hairs per day after COVID-19 infection, as well as half of the participants (52.6%) reported seeing hair accumulation on a pillow. Our results showed that telogen effluvium (TE) was the most reported type (156, 86.7%), followed by alopecia areata (15, 8.3%) and androgenic alopecia (9, 5.0%). Conclusion The results suggest that hair loss is noticeably prevalent in patients following COVID-19 infection, especially in females and patients with multiple comorbidities. Telogen effluvium (TE) was the most prevalent type of hair loss recognized among the patients.


Introduction
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in the city of Wuhan in China, and it spread around the world. It is transmitted rapidly among humans by Inhalation of respiratory droplets or contact [1,2]. When it comes to SARS-CoV-2 infection, it can present asymptomatically [3] and COVID-19 presentation can range from flu-like illness up to severe complications [4]. Furthermore, epidemiological studies showed that the elderly population was more susceptible to developing severe diseases, while children tend to have milder symptoms. It's currently a global pandemic that's hitting almost all countries. According to the WHO, one out of every 20 people will require intensive care, which may involve being sedated and placed on a ventilator [5]. Moreover, there are multiple variables that contribute to higher morbidity and mortality in COVID-19 infections such as diabetes, obesity, chronic obstructive pulmonary disease (COPD), advanced age, and male sex [6].
The consequences after recovery from COVID-19 infection have been of special concern. Therefore, researchers are investigating the phases beyond COVID-19 infection and have defined it as post-acute COVID-19 syndrome, which is characterized by persistent symptoms and/or delayed or long-term complications of SARS-CoV-2 infection beyond four weeks from the onset of symptoms that affect multiple organs. Here, we will focus on dermatological sequelae specifically hair loss [7]. Regarding the duration of the post-acute COVID-19 sequelae, it lasts for four weeks in a confirmed case. The two phases of a postacute COVID-19 syndrome are: first, the subacute phase that includes symptoms and abnormalities present from one to three months after acute COVID-19; second, chronic or post-COVID-19 syndrome, which 1 1 1 1 1 includes symptoms and abnormalities persisting or present after three months of the onset of acute COVID-19 and not attributable to alternative diagnoses [7].
In view of dermatological sequelae specifically hair loss, it is also described in the literature as telogen effluvium (TE). It occurs post COVID-19 infection by two mechanisms [8]. The first one is by direct damage of endothelial cells of small vessels by the virus, second is by indirect damage by the release of cytokines and development of immune inflammation around hair follicles and activation of coagulation cascade which leads to thrombus formation in the vessels that supply the hair follicles resulting in ischemia and necrosis of follicles [8]. Also, some medications such as antibiotics and anticoagulants can lead to TE [8].
The aim of this study is to measure the prevalence of hair loss after COVID-19 infection in Makkah region, Saudi Arabia, and we hope to improve the knowledge on hair loss -a cause of common dermatological consultation that frequently becomes a stressful event associated with the pandemic -among all the physicians in all the specialties.

Study design and patients' records
This was a multi-center, record-based retrospective cross-sectional study conducted in four centers in the Makkah region including King Abdulaziz Hospital, King Faisal Hospital, Heraa General Hospital, and Al-Noor Specialist Hospital. The study was conducted between January 2021 and March 2022. We identified 343 patients who visited the dermatology clinic for hair loss during the period 2020 to 2022. We enrolled patients of all age groups and only confirmed COVID-19 cases of both genders. On the other hand, we excluded 17 patients with iron deficiency anemia (IDA), post-partum female patients, and patients with a history of hair disorders.

Study database
Data for the analysis were obtained from the patient records who visited the dermatology clinic. The patient records contain sociodemographic information, past medical history of chronic disease, history of hair disorders before COVID-19, COVID-19 detection and history of hospitalization and medication used, and laboratory data for COVID-19 detection. Approval was obtained from the Institutional Review Board office of the Ministry of Health, Makkah (IRB Number: H-02-K-076-1021-580).

Definition of the confirmed cases of COVID-19 from a laboratory perspective
COVID-19 infection was defined according to the newly published paper as an integration of clinical characteristics, symptoms, and laboratory results. Regarding the new evidence of confirming COVID-19 cases, there were two tests: first, etiological diagnosis that may be direct, identifying genetic material of SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR); second was indirect test for determining the humoral immune response to SARS-CoV-2 by different serological tests [9].

Data analysis
After data were extracted, it was revised, coded, and fed to statistical software Statistical Package for the Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY). All statistical analysis was done using two-tailed tests. p-value less than 0.05 was statistically significant. Descriptive analysis based on frequency and percent distribution was done for all variables including patients' personal data, BMI, smoking, comorbidities and family history of alopecia. Also, patients' COVID-19 infection data were tabulated besides post-infection hair loss and alopecia-related frequency, types and duration. Crosstabulation was used to assess factors associated with post COVID-19 infection hair loss among study patients. Relations were tested using Pearson's chi-squared test and exact probability test for small frequency distributions.

Results
A total of 343 patients were enrolled in the study using a data collection sheet. Patients' ages ranged from 11 to 70 years with a mean age of 29. 5

Discussion
The current study was conducted to assess the prevalence of hair loss after COVID-19 infection in the Makkah region and the factors associated with post COVID-19 hair loss among study patients. In the present study, only confirmed COVID-19 cases were analyzed ( Table 2). There is increasing evidence suggesting that hair loss had been the most frequently reported post COVID-19 manifestation (2,800, 48%), from a total of 5,264 (89.4%) participants who were treated at home, 396 (6.7%) who were treated in a hospital, and 231 (3.9%) who were treated in an intensive care unit, according to a study conducted in Brazil [10]. In addition, a systematic review and meta-analysis aimed to assess the prevalence of long-term effects of COVID-19 on hair loss among 55 patients, and it was estimated to be one of the most common side effects of COVID-19 infection, with a prevalence of 25% [11], compared to our results that revealed nearly half of the participants (48.5%) noticed hair loss increases by more than 120 hairs per day after COVID-19 infection, as well as half of the participants (52.6%) reported seeing hair accumulation on a pillow ( Table 3). The significance of cutaneous involvement in COVID-19 was not recognized early in the pandemic but was discovered much later and was critical because it was a presenting complaint in some patients [12]. Müller-Ramos et al. discovered that telogen effluvium (TE) is the main cause of hair shedding after COVID-19 as a cutaneous involvement manifestation, and it has been reported in six previous studies, but because patients were not examined by a dermatologist, it was not possible to rule out other diagnoses (e.g., alopecia areata) [10].
Consequently, a study conducted in Turkey documented the increase in the prevalence of TE during the pandemic, and it was found in 27.9% of the 563 participants [13]. Moreover, according to Singh et al.'s systematic review, 25% of the 465 patients reported hair loss after recovering from COVID-19 and were later diagnosed with acute TE [14], that was in accordance with our results that showed telogen effluvium (TE) was the most reported type (156, 86.7%), followed by alopecia areata (15,8.3%) and androgenic alopecia (9, 5.0%) ( Table 3). Furthermore, in the present study, we found that 114 (63.3%) of patients experienced hair loss after 2-3 months of COVID-19 infection, whereas 43 (23.9%) experienced hair loss after six months of infection and 23 (12.8%) experienced hair loss immediately after infection ( Table 3). And this is similarly supported by a cross-sectional study that had been done among 39 patients with post COVID-19 hair loss confirmed by a hair pull test and they all reported severe hair loss within 2-3 months after infection [15].
Regarding the factors associated with post COVID-19 infection hair loss that has been reported in a multicenter study that shows the female gender, long hospital stays, a higher number of comorbidities, and a higher number of symptoms at hospital admission were risk factors associated with a higher number of post COVID-19 hair loss [16]. In the present study, most of the COVID-19 patients were female (261, 76.3%) ( Table 1), and there were different chronic diseases namely hypertension (20, 5.8%), diabetes mellitus (15,4.4%), respiratory disease (6, 1.8%), hypothyroidism (5, 1.5%), polycystic ovary syndrome (PCOS) (2, 0.6%), cardiovascular disease (2, 0.6%) and other reported chronic disease (Table 1). Similarly, the adjusted analysis revealed a significant value of the female gender factor (157, 60.2%) highly associated with the occurrence of hair loss on a pillow or during a shower after COVID-19 infection with (P = .001). Additionally, the presence of chronic disease (33, 61.1%) is a significant factor that plays a role in developing hair loss after COVID-19 infection with P = .049 ( Table 4). In an opposing view, the hospitalization due to COVID-19 infection mainly determines the severity of the COVID-19 infection, and it shows insignificant value regarding the factors associated with post COVID-19 infection hair loss with P = .417% means the severity of COVID-19 infection doesn't play a significant role in developing a hair loss (Table 4). However, we couldn't assess the severity of COVID-19 based on the hospital admission only, as it may require other clinical, radiological, and laboratory data that mainly determine the severity of the COVID-19 infection cases.
As a result of that, one of the recognized limitations of our study is it didn't collect objective measures of an admitted patient with COVID-19 such as inflammatory biomarkers, and blood oxygen saturation which mainly determines the severity of cases as well as the severity of development of cytokine storm and inflammatory response that is known mechanism to affect all the body cells in the form of post COVID-19 infection sequela. There are other limitations regarding the pictures of patients with hair loss that couldn't be taken to preserve the privacy of the enrolled patients.

Conclusions
COVID-19 infection is now a frequent and common cause of hair loss. Telogen effluvium (TE) is noticeably prevalent in patients following COVID-19 infection, especially in females and patients with multiple comorbidities. TE was the most prevalent type of hair loss recognized among the patients, and it's expected to occur 2-3 months post-infection. TE would be one of the important aspects of the long-term COVID-19 sequela, which will impact the quality of life of the affected person. As a result of that, we hope to improve the knowledge on hair loss -a cause of common dermatological consultation that frequently becomes a stressful event associated with the pandemic -among all the physicians in all specialties.
have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.