Статья
Витамин D как фактор повышения иммунитета и снижения риска развития острых респираторных вирусных инфекций и COVID-19
В период пандемии COVID-19 усилия исследователей во всем мире направлены на поиск профилактических и лечебных средств для борьбы с SARS-CoV-2. В последние несколько лет установлено, что дефицит витамина D может рассматриваться как один из возможных факторов риска развития и течения респираторной вирусной инфекции. Использование препаратов витамина D может быть оправдано с целью профилактики и лечения при комплексном подходе к терапии таких больных. В представленном обзоре обобщен материал по иммуномодулирующим свойствам витамина D, его роли в профилактике вирусных инфекций, включая новую коронавирусную инфекцию, а также механизмам снижения риска инфекции при помощи терапии витамином D. Надеемся, что данный обзор будет интересен не только эндокринологам, но и врачам смежных специальностей.
1. Zhu N, Zhang D, Wang W, Li X, Li X, Song J et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. doi:10.1056/NEJMoa2001017
2. Zhong NS, Zheng BJ, Li YM, Poon LLM, Xie ZH, Chan KH et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet. 2003;362(9393):1353–1358. doi.org/10.1016/S0140-6736(03)14630-2
3. Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369(5):407–416. doi:10.1056/NEJMoa1306742
4. Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019;11(1):59. doi:10.3390/v11010059
5. Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018;23(2):130–137. doi:10.1111/resp.13196
6. Zhao S, Lin Q, Ran J, Musa SS, Yang G, Wang W, Wang MH. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A datadriven analysis in the early phase of the outbreak. Int J Infect Dis. 2020;92:214–217. doi:10.1016/j.ijid.2020.01.050
7. Riley S, Fraser C, Donnley CA, Ghani AC, Abu-Raddad LJ, Hedley AJ, Chau P. Transmission dynamics of the etiological agents of SARS in Hong Kong: impact of public heals interventions. Science. 2003;300(5627):1961–1966. doi:10.1126/science.1086478
8. Пшеничная Н. Ю., Веселова Е. И., Семенова Д. А., Иванова С. С., Журавлев А. С. COVID-19 — новая глобальная угроза человечеству. Эпидемиология и инфекционные болезни. Актуальные вопросы. 2020;1:6–13. https://dx.doi.org/10.18565/epidem.2020.10.1.6–13
9. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE 2, the putative receptor of Wuhan 2019-n-Cov. BioRxiv. 2020. doi.org/10.1101/2020.01.26.919985
10. Kalil AC, Thomas PG. Influenza virus-related critical illness: Pathophysiology and epidemiology. Crit Care. 2019;23(1):258. doi:10.1186/s13054-019-2539-x
11. Holick MF. Vitamin D deficiency. N. Engl J Med. 2007;357(3):266–281. doi:10.1056/NEJMra070553
12. Beard JA, Bearden A, Striker R. Vitamin D and the antiviral state. J Clin Virol. 2011;50(3):194–200. doi:10.1016/j.jcv.2010.12.006
13. Hewison M. An update on vitamin D and human immunity. Clin Endocrinol. 2012;76(3):315–325. doi:10.1111/j.1365-2265.2011.04261.x
14. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D Nutrients. 2015;7(6):4240–4270. doi:10.3390/nu7064240
15. Wei R, Christakos S. Mechanisms underlying the regulation of innate and adaptive immunity by vitamin D. Nutrients. 2015;7(10):8251–8260. doi:10.3390/nu7105392
16. Coussens AK. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease. Photochem Photobiol Sci. 2017;16(3):314–338. doi:10.1039/c6pp00355a
17. Lang PO, Aspinall R. Vitamin D status and the host resistance to infections: what it is currently (not) understood. Clin Ther. 2017;39(5):930–945. doi:10.1016/j.clinthera.2017.04.004
18. Gruber-Bzura BM. Vitamin D and influenza-prevention or therapy? Int J Mol Sci. 2018;19(8):2419. doi:10.3390/ijms19082419
19. Rondanelli M, Miccono A, Lamburghini S, Avanzato I, Riva A, Allegrini P et al. Self-Care for common colds: the pivotal role of vitamin D, vitamin C, zinc, and Echinacea in three main immune interactive clusters (physical barriers, innate and adaptive immunity) involved during an episode of common colds-practical advice on dosages and on the time to take these nutrients/botanicals in order to prevent or treat common colds. Evid Based Complement Alternat Med. 2018;2018:5813095. doi:10.1155/2018/5813095
20. Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients. 2020;12(1):236. doi:10.3390/nu12010236
21. Sha Q, Truong-Tran A, Plitt J, Beck L, Schleimer R. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol. 2004;31.358–364.
22. Holt P, Strickland D, Wikström M, Jahnsen F. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol. 2008;8(2):142–152. doi:10.1038/nri2236
23. Malmgaard L, Melchjorsen J, Bowie A, Mogensen S, Paludan S. Viral activation of macrophages through TLR-dependent and -independent pathways. J Immunol. 2004;173;6890–6898.
24. Baeke F, Korf H, Overbergh L, Etten EV, Verstuyf A, Gysemans C et al. Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D 3 in the immune system. J Steroid Biochem Mol Biol. 2010;121(1–2):221–227. doi:10.1016/j.jsbmb.2010.03.037
25. Hewison M, Freeman L, Hughes S, Evans K, Bland R, Eliopoulos A et al. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol. 2003;170(11):5382–5390. doi.org/10.4049/jimmunol.170.11.5382
26. Ginde A, Mansbach J, Camargo C. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384–390. doi:10.1001/archinternmed.2008.560
27. White J. Regulation of intracrine production of 1,25-dihydroxyvitamin D and its role in innate immune defense against infection. Arch Biochem Biophys. 2012;523(1):58–63. doi:10.1016/j.abb.2011.11.006
28. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–1773. doi:10.1126/science.1123933
29. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF et al. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J. Immunol. 2009;82(7);4289–4295. doi:10.4049/jimmunol.0803736
30. Laaksi I. Vitamin D and respiratory infection in adults. Proc Nutr Soc. 2012;71(1);90–97. doi:10.1017/S0029665111003351
31. Agier J, Efenberger M, Brzezinska-Blaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol. 2015;40(2):225–235. doi:10.5114/ceji.2015.51359
32. Barlow PG, Svoboda P, Mackellar A, Nash AA, York IA, Pohl J et al. Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS ONE. 2011;6(10): e25333. doi:10.1371/journal.pone.0025333
33. Zhao Y, Ran Z, Jiang Q, Hu N, Yu B, Zhu L et al. Vitamin D alleviates Rotavirus infection through a microRNA - 155-5p mediated regulation of the TBK1/IRF3 signaling pathway in vivo and in vitro. Int J Mol Sci. 2019;20(14):3562. doi:10.3390/ijms20143562
34. Martinez-Moreno J, Hernandez J, Urcuqui-Inchima S. Effect of high doses of vitamin D supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles on dendritic cells. Mol Cell Biochem. 2020;464(1–2):169–180. doi:10.1007/s11010-019-03658-w
35. Колпакова А. Ф., Шарипов Р. Н., Латыева Е. Н., Колпаков Ф. А. Транскрипционный фактор NF-κB играет ключевую роль в регуляции генов, участвующих в воспалительных и иммунных реакциях. Сибирское медицинское обозрение. 2009;3(57):7–12.
36. Campbell P-A, Wu-Young M, Lee RC. Rapid response to Elisabeth Mahase E: Covid-19: what treatments are being investigated? Br Med J 2020;368: m1252. doi:10.1136/bmj.m1252. URL: www.bmj.com/content/368/bmj.m1252/rapid-responses
37. Lemire JM, Adams JS, Kermani-Arab V, Bakke AC, Sakai R, Jordan SC. 1,25-Dihydroxyvitamin D 3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol. 1985;134:3032–3035.
38. Cantorna MT, Snyder L, Lin YD, Yang L. Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients. 2015:7(4):3011–3021. doi:10.3390/nu7043011
39. Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison M et al. 1,25-Dihydroxyvitamin D 3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol. 2009;183(9):5458–5467. doi:10.4049/jimmunol.0803217
40. Colunga Biancatelli RML, Berrill M, Marik PE. The antiviral properties of vitamin C. Expert Rev Anti Infect. Ther. 2020;18(9):99–101. doi:10.1080/14787210.2020.1706483
41. Wimalawansa SJ. Global epidemic of coronavirus COVID-19: what we can do to minimze risks. Eur J Biomed Pharm Sci. 2020;7:432–438.
42. Vasarhelyi B, Satori A, Olajos F, Szabo A, Beko G. Low vitamin D levels among patients at Semmelweis University: Retrospective analysis during a one-year period. Orv Hetil. 2011;152(32):1272–1277. doi:10.1556/OH.2011.29187
43. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi:10.1016/S01406736(20)30183-5
44. Novel C. P.E.R.E. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Zhonghua Liu Xing Bing Xue Za Zhi 2020;41(2):145–151. doi:10.3760/cma.j.issn.0254-6450.2020.02.003
45. Kritchevsky SB, Tooze JA, Neiberg RH, Schwartz GG, Hausman DB, Johnson MA et al. 25-hydroxyvitamin D, parathyroid hormone, and mortality in black and white older adults: the health ABC study. J Clin Endocrinol Metab. 2012;97(11):4156–4165. doi:10.1210/jc.2012-1551
46. Hope-Simpson RE. The role of season in the epidemiology of influenza. J Hyg. 1981;86(1):35–47.
47. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129–1140. doi:10.1017/S0950268806007175e,hfnmnxr
48. Kroll MH, Bi C, Garber CC, Kaufman HW, Liu D, CastonBalderrama A et al. Temporal relationship between vitamin D status and parathyroid hormone in the United States. PLoS ONE. 2015;10(3):e0118108. doi:10.1371/journal.pone.0118108
49. Каронова Т. Л., Гринева Е. Н., Никитина И. Л., Цветкова Е. В., Тодиева А. М. и др. Уровень обеспеченности витамином D жителей Северо-Западного региона РФ (г. Санкт-Петербург и г. Петрозаводск). Остеопороз и остеопатии. 2013;16(3):3–7. doi:10.14341/osteo201333-7.
50. Петрушкина А. А., Пигарова Е. А., Рожтинская Л. Я. Эпидемиология дефицита витамина D в Российской Федерации. Остеопороз и остеопатии. 2018;21(3):15–20.
51. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. J Am Med Assoc. 2020. doi:10.1001/jama.2020.1585
52. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical course and risk factors for mortality of adult inpatients with COVID - 19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi:10.1016/S0140-6736(20)30566-3
53. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, John F Aloia JF, Peter Bergman P et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. Br Med J. 2017;356: i6583. doi.org/10.1136/bmj.i6583
54. Pham H, Rahman A, Majidi A, Waterhouse M, Rachel E, Neale RE. Acute respiratory tract infection and 25-hydroxyvitamin D concentration: a systematic review and meta-analysis. Int J Environ Res Public Health. 2019;16(17):3020. doi:10.3390/ijerph16173020
55. Zhou J, Du J, Huang L, Wang Y, Shi Y, Lin H. Preventive effects of vitamin D on seasonal influenza A in infants: a multicenter, randomized, open, controlled clinical trial. Pediatr Infect Dis J. 2018;37(8):749–754. doi:10.1097/INF.0000000000001890
56. Urashima M, Mezawa H, Noya M, Camargo CA Jr. Effects of vitamin D supplements on influenza A illness during the 2009 H1N 1 pandemic: a randomized controlled trial. Food Funct. 2014;5(9):2365–2370. doi:10.1039/c4fo00371c
57. Camargo C, Ganmaa D, Frazier A, Kirchberg F, Stuart J, Kleinman K et al. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics. 2012;130(3):561–567. doi:10.1542/peds.2011-3029
58. Berry DJ, Hesketh K, Power C, Hyppönen E. Vitamin D status has a linear association with seasonal infections and lung function in British adults. Br J Nutr. 2011;106(9):1433–40. doi:10.1017/S0007114511001991
59. Ginde AA, Blatchford P, Breese K, Zarrabi L, Linnebur SA, Wallace JI et al. High-dose monthly vitamin D for prevention of acute respiratory infection in older long-term care residents: a randomized clinical trial. J Am Geriatrics Soc. 2017;65(3):496–503. doi:10.1111/jgs.14679
60. Arihiro S, Nakashima A, Matsuoka M, Suto S, Uchiyama K, Kato T et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza and upper respiratory infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2019;25(6):1088–1095. doi:10.1093/ibd/izy346
61. Loeb M, Dang AD, Thiem VD, Thanabalan V, Wang B, Nguyen NB et al. Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: a randomized controlled trial. Influenza Other Respir Viruses. 2019;13(2):176–183. doi:10.1111/irv.12615
62. Laaksi I, Ruohola J, Mattila V, Auvinen A, Ylikomi T, Pihlajamäki H. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blinded trial among young Finnish men. J Infect Dis. 2010;202(5):809–814. doi:10.1086/654881
63. Li-Ng M, Aloia J, Pollack S, Cunha B, Mikhail M, Yeh J, Berbari N. A randomized controlled trial of vitamin D 3 supplementation for the prevention of symptomatic upper respiratory tract infections. Epidemiol Infect. 2009;137(10): 1396–1404. doi:10.1017/S0950268809002404
64. Jorde R, Witham M, Janssens W, Rolighed L, Borchhardt K, de Boer I et al. Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials. Scand J Infect Dis. 2012;44(2):126–132. doi:10.3109/00365548.2011.621446
65. Murdoch D, Slow S, Chambers S, Jennings L, Stewart A, Priest P et al. Effect of vitamin D 3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. J Am Med Assoc. 2012;308(13):13331339. doi:10.1001/jama.2012.12505
66. Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, Landry ML. Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS ONE. 2010;5(6): e11088. doi:10.1371/journal.pone.0011088
67. Martineau A, James W, Hooper R, Barnes N, Jolliffe D, Greiller C et al. Vitamin D 3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Lancet Respir Med. 2015;3(2):120–130. doi:10.1016/S2213-2600(14)70255-3
68. Han JE, Jones JL, Tangpricha V, Brown MA, Brown LAS, Hao L et al. High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial. J Clin Trans Endocrinol. 2016;4:59–65. doi:10.1016/j.jcte.2016.04.004
69. Delgado R, Fett C, Castaño-Rodriguez C, Perlman S, Enjuanes L. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014;88(2):913–24.
70. Cohen-Lahav M, Shany S, Tobvin D, Chaimovitz C, Douvdevani A. Vitamin D decreases NFκB activity by increasing IκBα levels. Nephrol Dialys Transplant. 2006;21(4):889–897. doi:10.1093/ndt/gfi254
71. Youssef DA, Ranasinghe T, Grant WB, Peiris AN. Vitamin D’s potential to reduce the risk of hospital-acquired infections. Dermatoendocrinol. 2012;4(2):167–175. doi:10.4161/derm.20789
72. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4):988. doi:10.3390/nu12040988
73. Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention of vitamin D deficiency: The Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi:10.1210/jc.2011-0385
74. Пигарова Е. А., Рожинская Л. Я., Белая Ж. Е., Дзеранова Л. К., Каронова Т. Л., Ильин А. В и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике, лечению и профилактике дефицита витамина D у взрослых. Проблемы эндокринологии. 2016;4:60–84. doi:10.14341/probl201662460-84.
75. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204–210. doi.org/10.1093/ajcn/77.1.204