Роли активных форм витамина D в поддержке систем врожденного иммунитета и снижении избыточного воспаления при COVID-19

Громова О.А., Торшин И.Ю., Чучалин А.Г., Кожевникова Е.Н., Малявская С.И. Роли активных форм витамина D в поддержке систем врожденного иммунитета и снижении избыточного воспаления при COVID-19. Терапевтический архив. 2021; 93 (8): 948–953. DOI: 10.26442/00403660.2021.08.200918

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Gromova OA, Torshin IIu, Chuchalin AG, Kozhevnikova EN, Malyavskaya SI. Roles of active forms of vitamin D in supporting innate immune systems and in reducing excess inflammation in COVID-19. Terapevticheskii Arkhiv (Ter. Arkh). 2021; 93 (8): 948–953.
DOI: 10.26442/00403660.2021.08.200918

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Аннотация

Сниженная обеспеченность микронутриентом витамином D приводит к более тяжелому течению коронавирусной инфекции (COVID-19). Недостаточность витамина D сочетается с понижением врожденного противовирусного иммунитета и избыточным воспалением. Дотации витамина D стимулируют синтез антибактериальных пептидов, они важны для ослабления цитокинового шторма, снижения избыточного острого и хронического воспаления, а также для компенсации хронических коморбидных патологий. Активные формы витамина D (альфакальцидол и др.) приобретают особое значение для компенсации недостаточности витамина D у пожилых пациентов, а также лиц с эндокринно-иммунной дисфункцией, саркопенией, хронической почечной недостаточностью (при которой нарушается метаболизм витамина D в почках).

Ключевые слова: COVID-19, противовирусный иммунитет, микронутриенты, альфакальцидол

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A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).

Keywords: COVID-19, antiviral immunity, micronutrients, alfacalcidol

Список литературы

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19. Huraib S, Tanimu D, Abu-Romeh S, et al. Effect of intravenous alfacalcidol on lymphocyte phenotyping in hemodialysis patients. Am J Kidney Dis. 1998;32(6):1036-40. DOI:10.1016/s0272-6386(98)70080-0
20. Zold E, Szodoray P, Nakken B, et al. Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease. Autoimmun Rev. 2011;10(3):155-62. DOI:10.1016/j.autrev.2010.09.018
21. Atsukawa M, Tsubota A, Shimada N, et al. Efficacy of Alfacalcidol on PEG-IFN/Ribavirin combination therapy for elderly patients with chronic hepatitis C: a pilot study. Hepat Mon. 2013;13(12):e14872. DOI:10.5812/hepatmon.14872
22. Su Y, Chen D, Yuan D, et al. Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19. Cell. 2020;183(6):1479-95.e20. DOI:10.1016/j.cell.2020.10.037
23. Торшин И.Ю., Громова О.А., Фролова Д.Е., и др. Дозозависимый хемотранскриптомный анализ дифференциального действия витамина D на экспрессию генов в клетках-предшественниках нейронов NPC и в опухолевых клетках MCF7 человека. Фармакокинетика и фармакодинамика. 2018;2:35-51 [Torshin IYu, Gromova OA, Frolova DE, et al. Dose-dependent chemotranscriptomics analysis of the differential effects of vitamin D on gene expression in human neuronal progenitor cells NPC and in MCF7 tumor cells. Pharmacokinetics and Pharmacodynamics. 2018;2:35-51 (in Russian)]. DOI:10.24411/2587-7836-2018-10013
24. Ali RM, Al-Shorbagy MY, Helmy MW, El-Abhar HS. Role of Wnt4/β-catenin, Ang II/TGFβ, ACE2, NF-κB, and IL-18 in attenuating renal ischemia/reperfusion-induced injury in rats treated with Vit D and pioglitazone. Eur J Pharmacol. 2018;831:68-76. DOI:10.1016/j.ejphar.2018.04.032
25. Yang X, Wu L, Li G, et al. Alphacalcidol combined with dexamethasone for reducing pulmonary fibrosis in mice and its mechanism. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33(4):488491. PMID: 28395719
26. Rizka A, Setiati S, Harimurti K, et al. Effect of Alfacalcidol on inflammatory markers and T cell subsets in elderly with frailty syndrome: a double blind randomized controlled trial. Acta Med Indones. 2018;50(3):215-21. PMID: 30333271
27. Liu C, Jiang ZC, Shao CX, et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study. Zhonghua Gan Zang Bing Za Zhi. 2020;28(2):148-52. DOI:10.3760/cma.j.issn.1007-3418.2020.02.003
28. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-7. DOI:10.1111/jth.14768
29. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in coronavirus disease 2019 patients: A systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-5. DOI:10.1016/j.ijid.2020.03.017
30. Ali AM, Selim S, Abbassi MM, Sabry NA. Effect of alfacalcidol on the pulmonary function of adult asthmatic patients: a randomized trial. Ann Allergy Asthma Immunol. 2017;118(5):557-63. DOI:10.1016/j.anai.2017.02.014
31. Abdel-Rehim WM, El-Tahan RA, El-Tarawy MA, et al. The possible antidiabetic effects of vitamin D receptors agonist in rat model of type 2 diabetes. Mol Cell Biochem. 2019;450(1-2):105-12. DOI:10.1007/s11010-018-3377-x
32. Ataie-Jafari A, Loke SC, Rahmat AB, et al. A randomized placebo-controlled trial of alphacalcidol on the preservation of beta cell function in children with recent onset type 1 diabetes. Clin Nutr. 2013;32(6):911-7. DOI:10.1016/j.clnu.2013.01.012
33. Mirzaei K, Hossein-Nezhad A, Keshavarz SA, et al. Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study. Minerva Med. 2014;105(1):63-78. PMID: 24572452
34. Ureña-Torres PA, Cozzolino M, Bover J. Utilization of alfacalcidol and active vitamin D analogs in chronic kidney disease. Nephrol Ther. 2018;14(4):189-200. DOI:10.1016/j.nephro.2017.03.003
35. Zand L, Kumar R. The Use of Vitamin D Metabolites and Analogues in the Treatment of Chronic Kidney Disease. Endocrinol Metab Clin North Am. 2017;46(4):983-1007. DOI:10.1016/j.ecl.2017.07.008
36. Громова О.А., Торшин И.Ю., Путилина М.В., и др. Ноцицепция: роли витамина D. Неврология, нейропсихиатрия, психосоматика. 2021;13(1):145-53 [Gromova OA, Torshin IYu, Putilina MV, et al. Nociception: the roles of vitamin D. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(1):145-53 (in Russian)]. DOI:10.14412/2074-2711-2021-1-145-153
37. Ringe JD, Farahmand P, Schacht E, Rozehnal A. Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial). Rheumatol Int. 2007;27(5):425-34. DOI:10.1007/s00296-006-0288-z
38. Ringe JD, Farahmand P, Schacht E. Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients. Rheumatol Int. 2013;33(3):637-43. DOI:10.1007/s00296-012-2429-x
39. Jørgensen HS, Winther S, Povlsen JV, Ivarsen P. Effect of vitamin-D analogue on albuminuria in patients with non-dialysed chronic kidney disease stage 4-5: a retrospective single center study. BMC Nephrol. 2012;13:102. DOI:10.1186/1471-2369-13-102

________________________________________________

1. Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020; 58(7):1116-20. DOI:10.1515/cclm-2020-0188
2. Wang Z, Yang B, Li Q, et al. Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020;71(15):769-77. DOI:10.1093/cid/ciaa272
3. Peng YD, Meng K, Guan HQ, et al. Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV. Zhonghua Xin Xue Guan Bing Za Zhi. 2020;48(0):E004. DOI:10.3760/cma.j.cn112148-20200220-00105
4. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol. 2020;5(7):831-40. DOI:10.1001/jamacardio.2020.1286. PMID: 32219363
5. Torshin IYu, Gromova OA. Ed. AG Chuchalin. Micronutrients against coronaviruses. Moscow: GEOTAR-Media, 2020 (in Russian)
6. Gromova OA, Torshin IYu. Vitamin D. Paradigm shift, 2nd ed., Revised. and add. Moscow: GEOTAR-Media, 2021 (in Russian)
7. De Smet D, De Smet K, Herroelen P, et al. Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality. Am J Clin Pathol. 2021;155(3):381-8. DOI:10.1093/ajcp/aqaa252. PMID: 33236114
8. Maghbooli Z, Sahraian MA, Ebrahimi M, et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS One. 2020;15(9):e0239799. DOI:10.1371/journal.pone.0239799
9. Hurwitz JL, Jones BG, Penkert RR, et al. Low retinol-binding protein and vitamin D levels are associated with severe outcomes in children hospitalized with lower respiratory tract infection and respiratory syncytial virus or human metapneumovirus detection. J Pediatr. 2017;187:323-7. DOI:10.1016/j.jpeds.2017.04.061
10. Gromova OA, Torshin IYu, Gabdulina GKh. COVID-19 pandemic: protective role of vitamin D. Farmakoekonomika. Modern Pharmacoeconomic and Pharmacoepidemiology. 2020;13(2):132-45 (in Russian) DOI:10.17749/2070-4909/farmakoekonomika.2020.044
11. Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D. J Autoimmun. 2017;85:78-97. DOI:10.1016/j.jaut.2017.07.007
12. Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state.
J Clin Virol. 2011;50(3):194-200. DOI:10.1016/j.jcv.2010.12.006
13. Charan J, Goyal JP, Saxena D, Yadav P. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. J Pharmacol Pharmacother. 2012;3(4):300-3. DOI:10.4103/0976-500X.103685
14. Grant WB, Goldstein M, Mascitelli L. Ample evidence exists from human studies that vitamin D reduces the risk of selected bacterial and viral infections. Exp Biol Med (Maywood). 2010;235(12):1395-6; discussion 1397. DOI:10.1258/ebm.2010.010c01
15. Wang G. Human antimicrobial peptides and proteins. Pharmaceuticals (Basel). 2014;7(5):545-94. DOI:10.3390/ph7050545
16. Vanherwegen AS, Gysemans C, Mathieu C. Regulation of Immune Function by Vitamin D and Its Use in Diseases of Immunity. Endocrinol Metab Clin North Am. 2017;46(4):1061-94. DOI:10.1016/j.ecl.2017.07.010
17. Vanherwegen AS, Gysemans C, Mathieu C. Vitamin D endocrinology on the cross-road between immunity and metabolism. Mol Cell Endocrinol. 2017;453:52-67. DOI:10.1016/j.mce.2017.04.018
18. Scherberich JE, Kellermeyer M, Ried C, Hartinger A. 1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro. Eur J Med Res. 2005;10(4):179-82. PMID: 15946915
19. Huraib S, Tanimu D, Abu-Romeh S, et al. Effect of intravenous alfacalcidol on lymphocyte phenotyping in hemodialysis patients. Am J Kidney Dis. 1998;32(6):1036-40. DOI:10.1016/s0272-6386(98)70080-0
20. Zold E, Szodoray P, Nakken B, et al. Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease. Autoimmun Rev. 2011;10(3):155-62. DOI:10.1016/j.autrev.2010.09.018
21. Atsukawa M, Tsubota A, Shimada N, et al. Efficacy of Alfacalcidol on PEG-IFN/Ribavirin combination therapy for elderly patients with chronic hepatitis C: a pilot study. Hepat Mon. 2013;13(12):e14872. DOI:10.5812/hepatmon.14872
22. Su Y, Chen D, Yuan D, et al. Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19. Cell. 2020;183(6):1479-95.e20. DOI:10.1016/j.cell.2020.10.037
23. Torshin IYu, Gromova OA, Frolova DE, et al. Dose-dependent chemotranscriptomics analysis of the differential effects of vitamin D on gene expression in human neuronal progenitor cells NPC and in MCF7 tumor cells. Pharmacokinetics and Pharmacodynamics. 2018;2:35-51 (in Russian) DOI:10.24411/2587-7836-2018-10013
24. Ali RM, Al-Shorbagy MY, Helmy MW, El-Abhar HS. Role of Wnt4/β-catenin, Ang II/TGFβ, ACE2, NF-κB, and IL-18 in attenuating renal ischemia/reperfusion-induced injury in rats treated with Vit D and pioglitazone. Eur J Pharmacol. 2018;831:68-76. DOI:10.1016/j.ejphar.2018.04.032
25. Yang X, Wu L, Li G, et al. Alphacalcidol combined with dexamethasone for reducing pulmonary fibrosis in mice and its mechanism. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33(4):488491. PMID: 28395719
26. Rizka A, Setiati S, Harimurti K, et al. Effect of Alfacalcidol on inflammatory markers and T cell subsets in elderly with frailty syndrome: a double blind randomized controlled trial. Acta Med Indones. 2018;50(3):215-21. PMID: 30333271
27. Liu C, Jiang ZC, Shao CX, et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study. Zhonghua Gan Zang Bing Za Zhi. 2020;28(2):148-52. DOI:10.3760/cma.j.issn.1007-3418.2020.02.003
28. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-7. DOI:10.1111/jth.14768
29. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in coronavirus disease 2019 patients: A systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-5. DOI:10.1016/j.ijid.2020.03.017
30. Ali AM, Selim S, Abbassi MM, Sabry NA. Effect of alfacalcidol on the pulmonary function of adult asthmatic patients: a randomized trial. Ann Allergy Asthma Immunol. 2017;118(5):557-63. DOI:10.1016/j.anai.2017.02.014
31. Abdel-Rehim WM, El-Tahan RA, El-Tarawy MA, et al. The possible antidiabetic effects of vitamin D receptors agonist in rat model of type 2 diabetes. Mol Cell Biochem. 2019;450(1-2):105-12. DOI:10.1007/s11010-018-3377-x
32. Ataie-Jafari A, Loke SC, Rahmat AB, et al. A randomized placebo-controlled trial of alphacalcidol on the preservation of beta cell function in children with recent onset type 1 diabetes. Clin Nutr. 2013;32(6):911-7. DOI:10.1016/j.clnu.2013.01.012
33. Mirzaei K, Hossein-Nezhad A, Keshavarz SA, et al. Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study. Minerva Med. 2014;105(1):63-78. PMID: 24572452
34. Ureña-Torres PA, Cozzolino M, Bover J. Utilization of alfacalcidol and active vitamin D analogs in chronic kidney disease. Nephrol Ther. 2018;14(4):189-200. DOI:10.1016/j.nephro.2017.03.003
35. Zand L, Kumar R. The Use of Vitamin D Metabolites and Analogues in the Treatment of Chronic Kidney Disease. Endocrinol Metab Clin North Am. 2017;46(4):983-1007. DOI:10.1016/j.ecl.2017.07.008
36. Gromova OA, Torshin IYu, Putilina MV, et al. Nociception: the roles of vitamin D. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(1):145-53 (in Russian)
DOI:10.14412/2074-2711-2021-1-145-153
37. Ringe JD, Farahmand P, Schacht E, Rozehnal A. Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial). Rheumatol Int. 2007;27(5):425-34. DOI:10.1007/s00296-006-0288-z
38. Ringe JD, Farahmand P, Schacht E. Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients. Rheumatol Int. 2013;33(3):637-43. DOI:10.1007/s00296-012-2429-x
39. Jørgensen HS, Winther S, Povlsen JV, Ivarsen P. Effect of vitamin-D analogue on albuminuria in patients with non-dialysed chronic kidney disease stage 4-5: a retrospective single center study. BMC Nephrol. 2012;13:102. DOI:10.1186/1471-2369-13-102

Авторы

О.А. Громова*1,2, И.Ю. Торшин1,2, А.Г. Чучалин3, Е.Н. Кожевникова4, С.И. Малявская2

1 ФИЦ «Информатика и управление» Российской академии наук, Москва, Россия;
2 ФГБОУ ВО «Северный государственный медицинский университет» Минздрава России, Архангельск, Россия;
3 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
4 ФГБНУ «Научно-исследовательский институт общей патологии и патофизиологии», Москва, Россия
*unesco.gromova@gmail.com

________________________________________________

Olga A. Gromova*1,2, Ivan Iu. Torshin1,2, Alexander G. Chuchalin3, Elena N. Kozhevnikova4, Svetlana I. Malyavskaya2

1 Computer Science and Control, Moscow, Russia;
2 Northern State Medical University, Arkhangelsk, Russia;
3 Pirogov Russian National Research Medical University, Moscow, Russia;
4 Institute of General Pathology and Pathophysiology, Moscow, Russia
*unesco.gromova@gmail.com

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