Vitamin D ve TMPRSS2: Post-COVID-19 Saç Dökülmesindeki Ortak Mekanizmalar

Abstract

Amaç: COVID-19 enfeksiyonunu takiben gelişen post-enfeksiyöz saç dökülmesi, önemli bir sekels olarak ortaya çıkmıştır. COVID-19 sonrasında bildirilen artmış telogen effluvium, androjenetik alopesi ve alopesi areata vakaları, immünolojik ve hormonal düzensizlikleri içeren multifaktöriyel bir patogenezi düşündürmektedir. Gereç ve Yöntem: COVID-19 enfeksiyonu ile saç dökülmesi arasındaki mekanistik yolakları incelemek amacıyla anlatı türünde bir literatür taraması gerçekleştirilmiştir. Çalışmada saç folikülü biyolojisi, immün modülasyon, hormonal sinyal yolları ve SARS-CoV-2’ye özgü hücre giriş mekanizmaları üzerine yayımlanmış hakemli makaleler değerlendirilmiştir. COVID-19 ilişkili alopesinin üç temel mekanizma üzerinden geliştiği saptanmıştır: (1) sitokin aracılı inflamasyonun saç folikül immün ayrıcalığını bozması, (2) androjen aracılı TMPRSS2 ekspresyonunun artmasıyla viral girişin kolaylaşması ve (3) virüsün foliküllere doğrudan hasar vermesi. Bulgular: Vitamin D, immün düzenleyici ve anti-androjenik özellikleri sayesinde proinflamatuar sitokinleri azaltmakta ve TMPRSS2 ekspresyonunu baskılamaktadır. Bu çift yönlü etki, viral invazyonu ve otoimmün kaynaklı saç dökülmesini azaltma potansiyeli taşımaktadır. Sonuç: Vitamin D, COVID-19 sonrası saç dökülmesinin önlenmesi veya hafifletilmesinde çift etkili bir strateji olarak öne çıkmaktadır. İnflamatuvar kaskadların baskılanması ve TMPRSS2 ekspresyonunun azaltılmasındaki rolü, gelecekte yapılacak klinik ve translasyonel araştırmalarla daha kapsamlı biçimde değerlendirilmelidir.

Keywords

• Covid-19
• TMPRSS2
• Vitamin D
• Alopesi
• Saç

Vitamin D And Tmprss2: Intersecting Pathways In Post-Covid-19 Alopecia

Abstract

Aim: Post-infectious hair loss has emerged as a notable sequela of SARS-CoV-2 infection. Reports of increased telogen effluvium, androgenetic alopecia, and alopecia areata following COVID-19 suggest a multifactorial pathogenesis involving immunological and hormonal dysregulation. Material and Methods: To review the mechanistic pathways linking COVID-19 infection with hair loss, with particular attention to the roles of cytokine-induced inflammation, androgen-regulated TMPRSS2 expression, and the potential protective function of vitamin D. A narrative literature review was conducted focusing on peer-reviewed publications discussing hair follicle biology, immune modulation, hormonal signaling, and viral entry mechanisms relevant to SARS-CoV-2. COVID-19-related alopecia is driven by (1) cytokine-mediated inflammation impairing follicular immune privilege, (2) androgen-enhanced Results: TMPRSS2 expression facilitating viral entry into follicular cells, and (3) direct follicular injury by the virus. Vitamin D exhibits immunoregulatory and anti-androgenic properties, reducing pro-inflammatory cytokines and downregulating TMPRSS2 expression, thus potentially mitigating both viral invasion and autoimmune hair loss. Conclusion: Vitamin D may offer a dual-action strategy in preventing or reducing post-COVID-19 hair loss. Its role in suppressing inflammatory cascades and TMPRSS2 expression warrants further investigation through clinical and translational research.

Keywords

• Covid 19
• TMPRSS2
• Vitamin D
• Alopecia
• Hair

Ethical Statement

This study that does not require ethics committee approval because it’s a review article.

References

1. 1. Hussain N, Agarwala P, Iqbal K, et al. A systematic review of acute telogen effluvium, a harrowing post-COVID-19 manifestation. J Med Virol 2022;94:1391–1401.
2. 2. Fivenson D. COVID-19: association with rapidly progressive forms of alopecia areata. Int J Dermatol 2020;60(1):127.
3. 3. Nguyen B, Tosti A. Alopecia in patients with COVID-19: a systematic review and meta-analysis. JAAD Int 2022;7:67–77.
4. 4. Sattur SS, Sattur IS. COVID-19 infection: impact on hair. Indian J Plast Surg 2021;54(4):521–526.
5. 5. Seyfi S, Alijanpour R, Aryanian Z, Ezoji K, Mahmoudi M. Prevalence of telogen effluvium hair loss in COVID-19 patients and its relationship with disease severity. J Med Life 2022;15(5):631.
6. 6. Rajabi F, Drake LA, Senna MM, Rezaei N. Alopecia areata: a review of disease pathogenesis. Br J Dermatol 2018;179:1033–1048.
7. 7. Salazar Arenas MA, Muñoz Del Carpio-Toia A, Aybar Galdos J, Rodriguez-Morales AJ. Alopecia and severity of COVID-19: a cross-sectional study in Peru. Infez Med 2021;29(1):37–45.
8. 8. Rossi A, Magri F, Michelini S, et al. Recurrence of alopecia areata after COVID-19 vaccination: a report of three cases. J Cosmet Dermatol 2021;20(12):3753-7.

9. 9. Tan Y, Tang F. SARS-CoV-2-mediated immune system activation and potential application in immunotherapy. Med Res Rev 2021;41:1167–1194.
10. 10. Adiguzel Y. Molecular mimicry between SARS-CoV-2 and human proteins. Autoimmun Rev 2021;20:102791.
11. 11. Kovacic D, Jotanovic J, Lakovic J. The possible role of molecular mimicry in SARS-CoV-2-mediated autoimmunity. J Med Sci 2021;90:e560.
12. 12. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer 2018;6:56.
13. 13. Iqbal NT, Khan H, Khalid A, et al. Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome. Mol Med 2025;31:22.
14. 14. Huang WY, Huang YC, Huang KS, et al. Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial–mesenchymal interaction. J Dermatol Sci 2017;86(2):114–122.
15. 15. Ghoreishi M, Martinka M, Dutz JP. Type 1 interferon signature in the scalp lesions of alopecia areata. Br J Dermatol 2010;163:57–62.
16. 16. Kabir Y, Goh C. Androgenetic alopecia: update on epidemiology, pathophysiology, and treatment. J Egypt Womens Dermatol Soc 2013;10:107–116.
17. 17. Ito T, Kageyama R, Nakazawa S, Honda T. Understanding cytokines and chemokines in alopecia areata. Exp Dermatol 2020;29:726–732.
18. 18. Kinori M, Bertolini M, Funk W, et al. CGRP may protect from interferon-γ-induced collapse of hair follicle immune privilege. Exp Dermatol 2012;21(3):223–226.
19. 19. Fehrholz M, Bertolini M. Collapse and restoration of hair follicle immune privilege ex vivo. Methods Mol Biol 2020;2154:133–141.
20. 20. Rossi A, Magri F, Sernicola A, et al. Telogen effluvium after SARS-CoV-2 infection. Skin Appendage Disord 2021;7(5):377–381.
21. 21. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2. Cell 2020;181:271–280.e8.
22. 22. Lv S, Wang L, Zou X. Acute telogen effluvium after SARS-CoV-2 infection. Clin Cosmet Investig Dermatol 2021;14:385–387.
23. 23. Salamanna F, Maglio M, Landini MP, Fini M. Body localization of ACE-2. Front Med 2020;7:594495.
24. 24. Wei KC, Huang MS, Chen TH. Dengue virus infection and hair follicle damage. Front Cell Infect Microbiol 2018;8:268.
25. 25. Cattrini C, Bersanelli M, Latocca MM, et al. Sex hormones during the COVID-19 pandemic. Cancers (Basel) 2020;12(8):2325.
26. 26. Montopoli M, Zumerle S, Vettor R, et al. Androgen-deprivation therapies and SARS-CoV-2 risk. Ann Oncol 2020;31(8):1040–1045.
27. 27. Wambier CG, Goren A, Vano-Galvan S, et al. Androgen sensitivity gateway to COVID-19 severity. Drug Dev Res 2020;81:771–776.
28. 28. Pourani MR, Nekooghadam SM, Youssefian L, et al. CD147 inhibitors and SARS-CoV-2. Dermatol Ther 2020;33:e14449.
29. 29. McCoy J, Wambier CG, Herrera S, et al. Androgen receptor variant predicts COVID-19 severity. J Eur Acad Dermatol Venereol 2021;35:e15–e17.
30. 30. Popescu MN, Berteanu M, Beiu C, et al. Complementary strategies to promote hair regrowth in post-COVID-19 telogen effluvium. Clin Cosmet Investig Dermatol 2022;15:735–743.
31. 31. Cadegiani FA, McCoy J, Wambier CG, et al. Proxalutamide accelerates viral clearance in COVID-19. Cureus 2021;13(2).
32. 32. Goren A, Wambier CG, Herrera S, et al. Anti-androgens and COVID-19 outcomes. J Eur Acad Dermatol Venereol 2021;35:e13–e15.
33. 33. Moravvej H, Pourani MR, Baghani M, Abdollahimajd F. Androgenetic alopecia and COVID-19. Dermatol Ther 2021;34:e15004.
34. 34. Mercola J, Grant WB, Wagner CL. Evidence regarding vitamin D and COVID-19. Nutrients 2020;12(11):3361.
35. 35. Ortatatli M, Fatsa T, Mulazimoglu DD, et al. Vitamin D, ACE2 and TMPRSS2 in COVID-19 severity. Arch Med Res 2023;54(3):223–230.
36. 36. Tsai TY, Huang YC. Vitamin D deficiency in alopecia areata. J Am Acad Dermatol 2018;78:207–209.
37. 37. Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. Vitamin D deficiency in alopecia areata. Br J Dermatol 2014;170:1299–1304.
38. 38. Mahamid M, Abu-Elhija O, Samamra M, et al. Vitamin D levels and alopecia areata. Isr Med Assoc J 2014;16:367–370.
39. 39. Yongpisarn T, Tejapira K, Thadanipon K, et al. Vitamin D deficiency in alopecia. Vitamin D: From Pathophysiology to Clinical Impact. Frontiers Media SA; 2025.
40. 40. Yilmaz N, Serarslan G, Gokce C. Vitamin D concentrations are decreased in alopecia areata. Vitam Miner 2012;1:105–109.
41. 41. Gade VKV, Mony A, Munisamy M, et al. Vitamin D status in alopecia areata. Clin Exp Med 2018;18:577–584.
42. 42. Sarac G, Koca TT. Importance of vitamin D in androgenic alopecia and telogen effluvium. J Clin Med Kazakhst 2018;50:26–29.
43. 43. Lin X, Meng X, Song Z. Vitamin D and alopecia areata. Am J Transl Res 2019;11(9):5285–5293.
44. 44. Jain A, Chaurasia R, Sengar NS, et al. Vitamin D levels in COVID-19 patients. Sci Rep 2020;10:20191.
45. 45. Greiller CL, Martineau AR. Immune modulation by vitamin D. Nutrients 2015;7:4240–4270.
46. 46. Wang TT, Dabbas B, Laperriere D, et al. Vitamin D and innate immunity. J Biol Chem 2010;285:2227–2231.
47. 47. Ashique S, Gupta K, Gupta G, et al. Vitamin D as immunomodulator in COVID-19. Int J Rheum Dis 2023;26(1):13–30.
48. 48. Ghelani D, Alesi S, Mousa A. Vitamin D and COVID-19 overview. Int J Mol Sci 2021;22(19):10559.
49. 49. Jose RJ, Manuel A. COVID-19 cytokine storm. Lancet Respir Med 2020;8:e46–e47.
50. 50. Cassell AK, Cassell LT, Bague AH. Cancer patient management during COVID-19. Artif Intell Cancer 2020;1(1):8–18.
51. 51. Bedair NI, Abdelaziz AS, Abdelrazik FS, et al. Post-COVID telogen effluvium. Arch Dermatol Res 2024;316(6):336.
52. 52. Visser MPJ, Dofferhoff ASM, van den Ouweland JMW, et al. Vitamin D and IL-6 in COVID-19. Front Nutr 2022;8:761191.
53. 53. Alruwaili MA, Jarrar Y. Vitamin C and D effects on ACE2 and TMPRSS2. Libyan J Med 2022;17(1).
54. 54. Kim JS, Roberts JM, Bingman WE III, et al. TMPRSS2-ERG and vitamin D receptor signaling. Endocrinology 2014;155(9):3262–3273.
55. 55. Song Y, Qayyum S, Greer RA, et al. Vitamin D3 derivatives against COVID-19. J Biomol Struct Dyn 2021;1–17.
56. 56. Glinsky GV. Vitamin D, quercetin, estradiol in COVID-19 mitigation. Biomedicines 2020;8:129.
57. 57. Kyrou I, Karteris E, Robbins T, et al. PCOS and COVID-19 risk. BMC Med 2020;18:220.
58. 58. Veskovic D, Ros T, Icin T, et al. Androgenetic alopecia and COVID-19 severity. Ir J Med Sci 2023;192:187–192.
59. 59. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients in China. N Engl J Med 2020;382:727–733.
60. 60. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3 as immunomodulator. Immunology 2011;134:123–139.
61. 61. Xu Z, Wang Y, Xiao ZG, et al. ERRα and ERG regulate TMPRSS2. Oncogene 2018;37(48):6259–6274.