The role of vitamin D in seasonal acute respiratory viral infections and COVID-19


Cite item

Full Text

Abstract

A link between vitamin D deficiency and susceptibility to infectious diseases was suggested over a hundred years ago. Epidemiological studies show a strong association between seasonal fluctuations in vitamin D levels and the incidence of various infectious diseases, including septic shock, acute respiratory infections, and influenza. Our understanding of vitamin D metabolism and its extra-skeletal functions has improved significantly over the past three decades, and the discovery that the vitamin D receptor and 1a-hydroxylase, an enzyme needed to convert vitamin D to its active form, is present in the cells of the immune system, revolutionized in this area. Recent studies have shown that vitamin D regulates the expression of specific endogenous antimicrobial peptides in immune cells, modulates the immune response and the course of autoimmune processes; these actions indicate the potential role of vitamin D in modulating the immune response to various infectious diseases. This publication reviews the literature on the effects of vitamin D on immunity, its potential in the prevention and treatment of viral diseases, with a particular focus on COVID-19.

About the authors

E. A. Pigarova

Endocrinology Research Centre

Author for correspondence.
Email: kpigarova@gmail.com
ORCID iD: 0000-0001-6539-466X

д.м.н., и.о. дир. Института высшего и дополнительного профессионального образования

Russian Federation, Moscow

A. A. Povalyaeva

Endocrinology Research Centre

Email: kpigarova@gmail.com
ORCID iD: 0000-0002-7634-5457

ассистент Центра аккредитации и симуляционного обучения Института высшего и дополнительного профессионального образования

Russian Federation, Moscow

L. K. Dzeranova

Endocrinology Research Centre

Email: kpigarova@gmail.com
ORCID iD: 0000-0002-0327-4619

д.м.н., гл. науч. сотр. отд-ния нейроэндокринологии и остеопатий

Russian Federation, Moscow

L. Y. Rozhinskaya

Endocrinology Research Centre

Email: kpigarova@gmail.com
ORCID iD: 0000-0001-7041-0732

д.м.н., проф., гл. науч. сотр. отд-ния нейроэндокринологии и остеопатий

Russian Federation, Moscow

N. G. Mokrysheva

Endocrinology Research Centre

Email: kpigarova@gmail.com
ORCID iD: 0000-0002-9717-9742

чл.-кор. РАН, д.м.н., дир.

Russian Federation, Moscow

References

  1. Fernandes AS, Lobo S, Sandes AR, et al. Vitamin D-dependent rickets: a resurgence of the rachitic lung in the 21st century. BMJ Case Rep. 2015 Oct 19;2015. pii: bcr2015212639. doi: 10.1136/bcr-2015-212639
  2. Dedicoat M. Where next with for vitamin D and tuberculosis? Int J Tuberc Lung Dis. 2020 Mar 1;24(3):265. doi: 10.5588/ijtld.20.0045
  3. Wang Y, Shi C, Yang Z, et al. Vitamin D deficiency and clinical outcomes related to septic shock in children with critical illness: a systematic review. Eur J Clin Nutr. 2019 Aug;73(8):1095-101. doi: 10.1038/s41430-018-0249-0
  4. Sundaram ME, Coleman LA. Vitamin D and influenza. Adv Nutr. 2012;3(4):517-25. doi: 10.3945/an.112.002162
  5. Пигарова Е.А., Плещева А.В., Дзеранова Л.К. Влияние витамина D на иммунную систему. Иммунология. 2015; 36(1):62-6 [Pigarova EA, Pleshcheva AV, Dzeranova LK. The effect of vitamin D on the immune system. Immunology. 2015;36(1):62-6 (In Russ.)].
  6. Koivisto O, Hanel A, Carlberg C. Key Vitamin D Target Genes with Functions in the Immune System. Nutrients. 2020 Apr 19;12(4). pii: E1140. doi: 10.3390/nu12041140
  7. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;10.1056/NEJMoa2001017. doi: 10.1056/NEJMoa2001017
  8. Zhong NS, Zheng BJ, Li YM, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet. 2003;362:1353-8. doi: 10.1016/s0140-6736(03)14630-2
  9. Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407-16. doi: 10.1056/NEJMoa1306742
  10. Song Z, Xu Y, Bao L, et al. From SARS to MERS, Thrusting Coronaviruses into the Spotlight. Viruses 2019, 11. doi: 10.3390/v11010059
  11. Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018;23:130-7. doi: 10.1111/resp.13196
  12. Britten R. The incidence of epidemic influenza, 1918–19. Public Health Rep. 1932;47:303-39.
  13. Лещенко И.В., Кривоногов А.В. Особенности течения пневмонии при пандемическом гриппе А/Н1N1/09. Пульмонология. 2011;6:62-8 [Leshchenko IV, Krivonogov AV. Features of the course of pneumonia in pandemic influenza А/Н1N1/09. Pulmonology. 2011;6:62-8 (In Russ.)]. doi: 10.18093/0869-0189-2011-0-6-62-68
  14. Плещева А.В., Пигарова Е.А., Дзеранова Л.К. Витамин D и метаболизм: факты, мифы и предубеждения. Ожирение и метаболизм. 2012;9(2):33-42 [Pleshcheva AV, Pigarova EA, Dzeranova LK. Vitamin D and metabolism: facts, myths and prejudices. Obesity and metabolism. 2012;9(2):33-42 (In Russ.)]. doi: 10.14341/omet2012233-42
  15. Пигарова Е.А., Мазурина Н.В., Трошина Е.А. Витамин D в профилактике костных и метаболических нарушений. Consilium Medicum. 2019;21(4):84-90 [Pigarova EA, Mazurina NV, Troshina EA. Vitamin D in the prevention of bone and metabolic disorders. Consilium Medicum. 2019;21(4):84-90 (In Russ.)]. doi: 10.26442/20751753.2019.4.190342
  16. Пигарова Е.А., Поваляева А.А., Дзеранова Л.К., Рожинская Л.Я. Роль витамина D для профилактики и лечения рахита у детей. Педиатрия. Consilium Medicum. 2019;3:40-5 [Pigarova EA, Povalyaeva AA, Dzeranova LK, Rozhinskaya LYa. The role of vitamin D in the prevention and treatment of rickets in children. Pediatrics. Consilium Medicum. 2019;3:40-5 (In Russ.)]. doi: 10.26442/20751753.2019.4.190342
  17. Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state. J Clin Virol. 2011;50:194-200. doi: 10.1016/j.jcv.2010.12.006
  18. Gruber-Bzura BM. Vitamin D and Influenza – Prevention or Therapy? Int J Mol Sci. 2018;19(8):2419. doi: 10.3390/ijms19082419
  19. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. 2015;7:4240-70. doi: 10.3390/nu7064240
  20. Odroważ-Sypniewska G, Karczmarewicz E, Paprotny Ł, Płudowski P. 3-epi-25(OH)D – A new metabolite, potential biological function, interference in laboratory assays. Stand Med Pediatr. 2012;9:680-6.
  21. Пигарова Е.А., Петрушкина А.А. Неклассические эффекты витамина D. Остеопороз и остеопатии. 2017;20(3):90-101 [Pigarova EA, Petrushkina AA. Nonclassical effects of vitamin D. Osteoporosis and bone diseases. 2017;20(3):90-101 (In Russ.)].
  22. Christakos S, Hewison M, Gardner DG, et al. Vitamin D: Beyond bone. Ann N Y Acad Sci. 2013;1287:45-58. doi: 10.1111/nyas.12129
  23. Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients. 2013;5:3993-4021. doi: 10.3390/nu5103993
  24. Петрушкина А.А., Пигарова Е.А., Рожинская Л.Я. Эпидемиология дефицита витамина D в Российской Федерации. Остеопороз и остеопатии. 2018;21(3):15-20 [Petrushkina AA, Pigarova EA, Rozhinskaya LYa. Epidemiology of Vitamin D Deficiency in the Russian Federation. Osteoporosis and bone diseases. 2018;21(3):15-20 (In Russ.)]. doi: 10.14341/osteo10038
  25. Пигарова Е.А. Основные положения клинических рекомендаций Российской Ассоциации Эндокринологов «Дефицит витамина D у взрослых: диагностика, лечение и профилактика». Остеопороз и остеопатии. 2015;18 (2):29-32 [Pigarova EA. The main provisions of the clinical recommendations of the Russian Association of Endocrinologists «Vitamin D deficiency in adults: diagnosis, treatment and prevention». Osteoporosis and bone diseases. 2015;18(2):29-32 (In Russ.)].
  26. Cashman KD, Sheehy T, O’Neill CM. Is vitamin D deficiency a public health concern for low middle income countries? A systematic literature review. Eur J Nutr. doi: 10.1007/s00394-018-1607-3
  27. Papadimitriou DT. The Big Vitamin D Mistake. J Prev Med Public Health. 2017 Jul;50(4):278-81. doi: 10.3961/jpmph.16.111
  28. Пигарова Е.А., Поваляева А.А., Дзеранова Л.К., Рожинская Л.Я. Роль витамина D в профилактике и лечении остеопороза – новый взгляд на известную проблему. Рус. мед. журнал. Медицинское обозрение. 2019;3(10-2):102-6 [Pigarova EA, Povalyaeva AA, Dzeranova LK, Rozhinskaya LYa. The role of vitamin D in the prevention and treatment of osteoporosis is a new look at a known problem. Rus honey. magazine. Medical Review. 2019;3(10-2):102-6 (In Russ.)].
  29. Kara M, Ekiz T, Ricci V, et al. ‘Scientific Strabismus’ or Two Related Pandemics: COVID-19 & Vitamin D Deficiency. Br J Nutr. 2020;1-20. doi: 10.1017/S0007114520001749
  30. Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol. 2013;136:321-9. doi: 10.1016/j.jsbmb.2012.11.017
  31. Schwalfenberg GK. A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency. Mol Nutr Food Res. 2011;55:96-108. doi: 10.1002/mnfr.201000174
  32. Laaksi I. Vitamin D and respiratory infection in adults. Proc Nutr Soc. 2012;71:90-7. doi: 10.1017/S0029665111003351
  33. Ross GA, Fanous H, Colin AA. Viral strategies predisposing to respiratory bacterial superinfections. Pediatr Pulmonol. 2020. doi: 10.1002/ppul.24699
  34. Agier J, Efenberger M, Brzezinska-Blaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol. 2015;40:225-35. doi: 10.5114/ceji.2015.51359
  35. Grant WB, Lahore H, McDonnell SL, 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
  36. Herr C, Shaykhiev R, Bals R. The role of cathelicidin and defensins in pulmonary inflammatory diseases. Expert Opin Biol Ther. 2007;7:1449-61. doi: 10.1517/14712598.7.9.1449
  37. Szymczak I, Pawliczak R. The active metabolite of vitamin D3 as a potential immunomodulator. Scand J Immunol. 2015;83:83-91. doi: 10.1111/sji.12403
  38. Bikle DD. Extraskeletal actions of vitamin D. Ann N Y Acad Sci. 2016;1376:29-51. doi: 10.1111/nyas.13219
  39. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. 2015;7:4240-70. doi: 10.3390/nu7064240
  40. Handel AE, Sandve GK, Disanto G, et al. Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease. BMC Med. 2013;11:163. doi: 10.1186/1741-7015-11-163
  41. Kongsbak M, von Essen MR, Levring TB, et al. Vitamin D-binding protein controls T cell responses to vitamin D. BMC Immunol. 2014;15:35. doi: 10.1186/s12865-014-0035-2
  42. Ooi JH, McDaniel KL, Weaver V, Cantorna MT. Murine CD8+ T cells but not macrophages express the vitamin D 1alpha-hydroxylase. J Nutr Biochem. 2014;25:58-65. doi: 10.1016/j.jnutbio.2013.09.003
  43. Lee MD, Lin CH, Lei WT, et al. Does Vitamin D Deficiency Affect the Immunogenic Responses to Influenza Vaccination? A Systematic Review and Meta-Analysis. Nutrients. 2018;10(4):409. doi: 10.3390/nu10040409
  44. Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J. 2019;16:69. doi: 10.1186/s12985-019-1182-0
  45. Ramos-Martínez E, López-Vancell MR, Fernández de Córdova-Aguirre JC, et al. Reduction of respiratory infections in asthma patients supplemented with vitamin D is related to increased serum IL-10 and IFNγ levels and cathelicidin expression. Cytokine. 2018;108:239-46. doi: 10.1016/j.cyto.2018.01.001
  46. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5
  47. 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):507-13. doi: 10.1016/S0140-6736(20)30211-7
  48. Available from: https://www.bbc.com/russian/features-52839688
  49. Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020;117(20):10970-5. doi: 10.1073/pnas.2005615117
  50. Parlak E, Ertürk A, Çağ Y, et al. The effect of inflammatory cytokines and the level of vitamin D on prognosis in Crimean-Congo hemorrhagic fever. Int J Clin Exp Med. 2015;8:18302-10.
  51. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X
  52. Shi Y, Liu T, Yao LI, et al. Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system. Sci Rep. 2017;7(1):3312. doi: 10.1038/s41598-017-03474-6
  53. Hanff TC, Harhay MO, Brown TS, et al. Is there an association between COVID-19 mortality and the renin-angiotensin system – a call for epidemiologic investigations. Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa329
  54. 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. doi: 10.1001/jama.2020.1585
  55. Mohammad S, Mishra A, Ashraf MZ. Emerging role of vitamin D and its associated molecules in pathways related to pathogenesis of thrombosis. Biomolecules. 2019;9(11):649. doi: 10.3390/biom9110649
  56. Laird E, Rhodes J, Kenny RA. Vitamin D and Inflamation; potential implications for severity of Covid-19. Ir Med J. 2020;113(5):P81.
  57. Marik PE, Kory P, Varon J. Does vitamin D status impact mortality from SARS-CoV-2 infection? Med Drug Discov. 2020;100041. doi: 10.1016/j.medidd.2020.100041
  58. D’Avolio A, Avataneo V, Manca A, et al. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients. 2020;12(5):E1359. doi: 10.3390/nu12051359
  59. Alipio M. Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19) (April 9, 2020). https://ssrn.com/abstract=3571484 or http://dx.doi.org/10.2139/ssrn.3571484
  60. Raharusun P, Sadiah P, Budiarti C, et al. Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study (April 26, 2020). https://ssrn.com/abstract=3585561 or http://dx.doi.org/10.2139/ssrn.3585561
  61. Jakovac H. COVID-19 and vitamin D-Is there a link and an opportunity for intervention? Am J Physiol Endocrinol Metab. 2020;318(5):E589. doi: 10.1152/ajpendo.00138.2020
  62. Лесняк О.М., Никитинская О.А., Торопцова Н.В. и др. Профилактика, диагностика и лечение дефицита витамина D и кальция у взрослого населения России и пациентов с остеопорозом (по материалам подготовленных клинических рекомендаций). Научно-практическая ревматология. 2015;53(4):403-8 [Lesnyak OM, Nikitinskaya OA, Toroptsova NV, et al. The prevention, diagnosis, and treatment of vitamin D and calcium deficiencies in the adult population of Russia and in patients with osteoporosis (according to the materials of prepared clinical recommendations). Scientific and practical rheumatology. 2015;53(4):403-8 (In Russ.)]. doi: 10.14412/1995-4484-2015-403-408
  63. Пигарова Е.А., Рожинская Л.Я., Белая Ж.Е. и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике, лечению и профилактике дефицита витамина D у взрослых. Проблемы эндокринологии. 2016;62(4):60-84 [Pigarova EA, Rozhinskaya LYa, Belaya ZhE, et al. Russian Association of Endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults. Problems of endocrinology. 2016;62(4):60-84 (In Russ.)]. doi: 10.14341/probl201662460-84
  64. Heaney RP, Davies KM, Chen TC, et al. Human serum 25-hydroxychole-calciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204-10. doi: 10.1093/ajcn/77.1.204

Copyright (c) 2020 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies