Covid-19’da Cinsiyet Hormonlarının İmmün Yanıt Üzerine Etkileri

Yıl 2021, Cilt: 47 Sayı: 3, 477 - 482, 01.12.2021

Ayşegül Yılmaz , Demet Kaçaroğlu , Yasemin Atıcı , Hilal Şamandar Aydaş

https://doi.org/10.32708/uutfd.1003159

Cited By: 3

Öz

Koronavirüs hastalığı 2019 (COVID-19), şiddetli akut solunum sendromu koronavirüs 2'nin (SARS-CoV-2) neden olduğu özellikle akciğerde şiddetli doku hasarına neden olan, yoğun inflamatuvar yanıt oluşturan bulaşıcı bir hastalıktır. Yapılan çalışmalar, COVID-19 enfeksiyonu olan erkeklerin kadınlara göre daha şiddetli semptomlar gösterdiği, yaşlı popülasyonunda COVID-19'dan ölüm riskinin gençlere göre daha yüksek olduğu bildirilmiştir. Erkeklerde COVID-19’un kadınlara göre daha ciddi seyretmesi, cinsiyet hormonlarının bu duruma etkisinin olabileceğini düşündürmektedir. Kadın ve erkeklerde cinsiyet hormon seviyelerindeki farklılık immün yanıtları önemli derecede etkilemektedir. COVID-19 pandemisinin sağlık sistemleri ve küresel ekonomi üzerindeki etkileri göz önüne alındığında, yenilikçi tedavi stratejilerine ihtiyaç duyulmaktadır. Bu doğrultuda, cinsiyet hormon terapileri COVID-19 hastaları için umut verici terapötik stratejiler sağlayabilir. Bu derlemede, COVID-19 enfeksiyonu prognozunda etkili olabilecek cinsiyet hormonlarının immün sistemdeki etkileri ve tedavi stratejileri üzerine yapılan çalışmalar incelenmiştir. Cinsiyet hormonlarının immün sistem üzerindeki etkileri dikkate alınarak uygulanan hormon tedavilerinin klinisyenlere yol göstereceğini ve COVID-19 tedavi protokollerine katkı sağlayacağını düşünmekteyiz.

Anahtar Kelimeler

COVID-19, SARS-CoV-2, cinsiyet hormonları, immün yanıt, hormon tedavisi

Effects of Sex Hormones on Immune Response in Covid-19

Öz

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that produces an intense inflammatory response, causing severe tissue damage, especially in the lung. Studies have reported that men with COVID-19 infection show more severe symptoms than women, and the risk of death from COVID-19 in the elderly population is higher than young people. The fact that COVID- 19 is more serious in men than in women suggests that sex hormones may have an effect on this situation. Differences in sex hormone levels in men and women significantly affect immune responses. Considering the effects of the COVID-19 pandemics on health systems and the global economy, innovative treatment strategies are needed. Accordingly, sex hormone therapies may provide promising therapeutic strategies for COVID-19 patients. In this review, studies on the effects of sex hormones on the immune system and treatment strategies that may be effective in the prognosis of COVID-19 infection were examined. Considering the effects of sex hormones on the immune system, we think that application of hormone treatment may be a guide for clinicians and contribute to COVID-19 treatment protocols.

Anahtar Kelimeler

COVID-19, SARS-CoV-2, sex hormones, immune response, hormone therapy

Kaynakça

• 1. Zhou P, Yang XL, Wang XG et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273.
• 2. Gorbalenya AE, Baker SC, Baric RS et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5, 536–544.
• 3. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242.
• 4. coronavirus.jhu.edu/map.html [homepage on the Internet]. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) [updated 22 September 2021]. www.coronavirus.jhu.edu/map.html
• 5. Richardson S, Hirsch JS, Narasimhan M et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20):2052-2059.
• 6. Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA. 2020;323(14):1335.
• 7. Chen N, Zhou M, Dong X et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.
• 8. Li Q, Guan X, Wu P et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-1207.
• 9. Yang X, Yu Y, Xu J et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-481.
• 10. Meng Y, Wu P, Lu W et al. Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients. PLoS Pathog. 2020 Apr 28;16(4):e1008520.
• 11. Gebhard C, Regitz-Zagrosek V, Neuhauser HK et al.Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ. 2020;11(1):29.
• 12. Atıcı Y, Elbaş Y, Bakır F, Yıldırımkaya MM. COVID-19 enfeksiyonunda ACE ve ACE2 reseptörlerinin potansiyel rolü. Yücel D, editör. COVID-19 Pandemisinde Tıbbi Biyokimyanın Artan Rolü. 1. Baskı. Ankara: Türkiye Klinikleri; 2021:57-62.
• 13. Sellau J, Groneberg M, Lotter H. Androgen-dependent immune modulation in parasitic infection. Semin Immunopathol. 2019;41(2):213-224.
• 14. Taneja V. Sex Hormones Determine Immune Response. Front Immunol. 2018;27(9):1931.
• 15. Pivonello R, Auriemma RS, Pivonello C et al. Sex Dısparıtıes In Covıd-19 Severıty And Outcome: Are Men Weaker or Women Stronger? Neuroendocrinology. 2020 Nov 26:1–20.
• 16. Straub R.H. The complex role of estrogens in inflammation. Endocr Rev 2007; 28:521-574.
• 17. Pontecorvi G, Bellenghi M, Ortona E et al. microRNAs as new possible actors in gender disparities of COVID-19 pandemic. Acta Physiol. 2020;230:e13538.
• 18. Kumar RS, Goyal N. Estrogens as regulator of hematopoietic stem cell, immune cells and bone biology. Life Sci. 2021;269:119091.
• 19. Medina-Estrada I, Alva-Murillo N, López-Meza JE et al. Immunomodulatory Effects of 17β-Estradiol on Epithelial Cells during Bacterial Infections. J Immunol Res. 2018;2018:6098961.
• 20. Blakemore J, Naftolin F. Aromatase: Contributions to Physiology and Disease in Women and Men. Physiology (Bethesda). 2016;31(4):258-69.
• 21. Patel S, Homaei A, Raju AB et al. Estrogen: The necessary evil for human health, and ways to tame it. Biomed Pharmacother. 2018;102:403-411.
• 22. Bhatia A, Sekhon HK, Kaur G. Sex hormones and immune dimorphism. Scientific World Journal. 2014; 1–8.
• 23. Altunkaynak BZ, Ünal D,Aksak S,Ünal B. Östrojen Hormonu Ve Menopoz. Ondokuz Mayis Universitesi Tip Dergisi. 2012; 29(4):252–256.
• 24. Koenig A, Buskiewicz I, Huber SA. Age-associated changes in estrogen receptor ratios correlate with increased female susceptibility to coxsackievirus B3-induced myocarditis, Frontiers in Immunology. 2017;16(8):1585.
• 25. Cady N, Peterson SR, Freedman SN et al. Beyond Metabolism: The Complex Interplay Between Dietary Phytoestrogens, Gut Bacteria, and Cells of Nervous and Immune Systems. Frontiers in Neurology. 2020;11:150.
• 26. Lee TP, Chiang BL. Sex differences in spontaneous versus induced animal models of autoimmunity. Autoimmun Rev. 2012;11(6-7):A422-9.
• 27. Klein SL, Marriott I, Fish EN. Sex-based differences in immune function and responses to vaccination. Trans R Soc Trop Med Hyg. 2015;109(1):9-15.
• 28. Mauvais-Jarvis F, Klein SL, Levin ER. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology. (2020);161(9):1–8.
• 29. Ghosh S, Klein RS. ‘Sex Drives Dimorphic Immune Responses to Viral Infections. The Journal of Immunology. 2017;198(5):1782–1790.
• 30. González DA, Díaz BB, Rodríguez Pérez Mdel C et al. Sex hormones and autoimmunity. Immunol Lett. 2010;6,133(1):6-13.
• 31. Raza HA, Sen P, Bhatti OA et al. Sex hormones, autoimmunity and gender disparity in COVID-19. Rheumatol Int. 2021;41(8):1375-1386.
• 32. Wang Z, Pan H, Jiang B. Type I IFN deficiency: an immunological characteristic of severe COVID-19 patients. Signal Transduct Target Ther. (2020);5(1):198.
• 33. Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases. Current Opinion in Rheumatology. 2021; 33(2):155–162.
• 34. Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nature Medicine. 2021;27(1): 28–33.
• 35. Garg R, Agrawal P, Gautam A et al. A. COVID-19 Outcomes in Postmenopausal and Perimenopausal Females: Is Estrogen Hormone Attributing to Gender Differences? J Midlife Health. 2020;11(4):250-256.
• 36. Pardhe, B. D., Ghimire, S., Shakya, J et. al. Elevated Cardiovascular Risks among Postmenopausal Women: A Community Based Case Control Study from Nepal. Biochemistry Research International. 2017; Article ID 3824903.
• 37. Bansal M. Cardiovascular disease and COVID-19. Diabetes & Metabolic Syndrome. 2020;14(3):247–250.
• 38. Klein SL. Morgan R. The impact of sex and gender on immunotherapy outcomes. Biology of Sex Differences. 2020;11(1):1–13.
• 39. Kadel S, Kovats S. Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection. Front Immunol. 2018;9:1653.
• 40. Ghare Naz MS, Banaei M, Dashti S et al. An overview of sex hormones in relation to SARS-CoV-2 infection. Future Virol. 2021;Jul:10.2217/fvl-2021-0058.
• 41. Klein SL, Flanagan KL.Sex differences in immune responses. Nature Reviews Immunology. 2016;16(10):626–638.
• 42. Hall OJ, Limjunyawong N, Vermillion MS et al. Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females. PLoS Pathog. 2016;12(9):e1005840.
• 43. Marchetti PM, Barth JH. Clinical biochemistry of dihydrotestosterone. Ann Clin Biochem. 2013;(50):95-107.
• 44. Davey RA,Grossmann M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. The Clinical Biochemist. Reviews. 2016;37(1):3–15.
• 45. Tzanakakis G, Giatagana EM, Kuskov A et al. Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors. Cancers (Basel). 2020;12(9):2401.
• 46. Billi AC, Kahlenberg JM, Gudjonsson JE. Sex bias in autoimmunity. Curr Opin Rheumatol. (2019);31(1):53-61.
• 47. Traish A, Bolanos J, Nair S et al. Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence. J Clin Med. 2018;7(12):549.
• 48. Jeremy M. Auerbach MK.Testosterone’s Role in COVID-19. The Journal of Sexual Medicine. 2021;18,(5):843–848.
• 49. Baillargeon J, Al Snih S, Raji MA et al. Hypogonadism and the risk of rheumatic autoimmune disease. Clin Rheumatol. 2016;35(12):2983-2987.
• 50. Rastrelli G, Di Stasi V, Inglese F et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology. 2021;9(1):88-98.
• 51. Wang D, Hu B, Hu C et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069.
• 52. Li H, Manwani B, Leng SX. Frailty, inflammation, and immunity. Aging Dis. 2011;2(6):466-73.
• 53. Pozzilli P, Lenzi A. Commentary: Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism. 2020; Jul(108):154252.
• 54. Hussain AN, Hussain F, Hashmi SK. Role of testosterone in COVID-19 patients- A double-edged sword? Med Hypotheses. 2020; Nov(144):110287.
• 55. Mjaess G, Karam A, Aoun F et al. COVID-19 and the male susceptibility: the role of ACE2, TMPRSS2 and the androgen receptor. Prog Urol. 2020;30(10):484-487.
• 56. Stopsack KH, Mucci LA, Antonarakis ES et al. TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention? Cancer Discov. 2020;10(6):779-782.
• 57. Li G, He X, Zhang L et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmun. 2020; Aug(112):102463.
• 58. Jin JM, Bai P, He W et al. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health. 2020;29(8):152.
• 59. Li MY, Li L, Zhang Y et al. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020;9(1):45.
• 60. Kopel J, Perisetti A, Roghani A et al. Racial and Gender-Based Differences in COVID-19. Front Public Health. 2020;8:418.
• 61. Molloy EJ, O'Neill AJ, Grantham JJ et al. Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone. Blood. 2003;102(7):2653-9.
• 62. Al-Lami RA, Urban RJ, Volpi E et al. Sex Hormones and Novel Corona Virus Infectious Disease (COVID-19). Mayo Clin Proc. 2020;95(8):1710-1714.
• 63. Sanders JM, Monogue ML, Jodlowski TZ et al. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;323(18):1824-1836.
• 64. Ramírez I, De la Viuda E, Baquedano L et al. Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia. Maturitas. 2020;Jul(137):57-62.
• 65. Gennadi, G. Vitamin D and Quercetin manifest properties of candidate medicinal agents for mitigation of the severity of pandemic COVID-19 defined by genomics-guided tracing of SARS-CoV-2 targets in human cells. Biomedicines.2020;8(5):129.
• 66. Zhao Y, Ren J, Harlos K et al. Toremifene interacts with and destabilizes the Ebola virus glycoprotein. Nature. 2016;535(7610):169-172.
• 67. Corrales JJ, Almeida M, Burgo R et al. Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men and partial androgen deficiency. Journal of Endocrinology. 2006;189(3), 595–604.
• 68. Salciccia S, Del Giudice F, Eisenberg ML et al. Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection. Ther Adv Endocrinol Metab. 2021;12:20420188211010105.
• 69. Montopoli M, Zumerle S, Vettor R et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020:1040-1045.
• 70. Salciccia S, Del Giudice F, Gentile V et al. Interplay between male testosterone levels and the risk for subsequent invasive respiratory assistance among COVID-19 patients at hospital admission. Endocrine. 2020;70(2):206-210.
• 71. Haitao T, Vermunt JV, Abeykoon J et al. COVID-19 and Sex Differences: Mechanisms and Biomarkers. Mayo Clin Proc. 2020;95(10):2189-2203.