Pediatrics. Consilium MedicumPediatrics. Consilium MedicumПедиатрия. Consilium Medicum2658-66302658-6622Consilium Medicum10954510.26442/26586630.2022.2.201682ArticlesСтатьиReview ArticleVitamin D as the essential immunonutrient – the evidence base update: A reviewВитамин D как эссенциальный иммунонутриент – обновление доказательной базыhttps://orcid.org/0000-0002-3056-403XMakarovaSvetlana G.МакароваСветлана Геннадиевна
Russian Federation

D. Sci. (Med.), National Medical Research Center for Children's Health, Lomonosov Moscow State University

д-р мед. наук, зам. дир. по научной работе, рук. Центра профилактической педиатрии ФГАУ «НМИЦ здоровья детей», проф. каф. многопрофильной клинической подготовки фак-та фундаментальной медицины ФГБОУ ВО «МГУ им. М.В. Ломоносова»

sm27@yandex.ruhttps://orcid.org/0000-0002-0995-4260EmelyashenkovEvgeny E.ЕмельяшенковЕвгений Евгеньевич
Russian Federation

Graduate Student, National Medical Research Center for Children's Health

аспирант ФГАУ «НМИЦ здоровья детей»

dkswdsman@mail.ruhttps://orcid.org/0000-0003-1330-2828YasakovDmitry S.ЯсаковДмитрий Сергеевич
Russian Federation

Cand. Sci. (Med.), National Medical Research Center for Children's Health

канд. мед. наук, ст. науч. сотр. отд. профилактической педиатрии ФГАУ «НМИЦ здоровья детей»

dmyasakov@mail.ruhttps://orcid.org/0000-0003-3306-6869ProninaIrina Yu.ПронинаИрина Юрьевна
Russian Federation

Res. Assist., National Medical Research Center for Children's Health, Endocrinology Research Centre

мл. науч. сотр., врач-диетолог отд. профилактической педиатрии ФГАУ «НМИЦ здоровья детей», врач-эндокринолог Группы доклинического сопровождения ФГБУ «НМИЦ эндокринологии»

krapchatovaiv@yandex.ruhttps://orcid.org/0000-0002-1650-652XEreshkoOksana A.ЕрешкоОксана Александровна
Russian Federation

Cand. Sci. (Med.), National Medical Research Center for Children's Health

канд. мед. наук, врач-аллерголог, ст. науч. сотр. отд. профилактической педиатрии ФГАУ «НМИЦ здоровья детей»

sm27@yandex.ruhttps://orcid.org/0000-0001-6658-0624GordeevaIrina G.ГордееваИрина Григорьевна
Russian Federation

Res. Assist., National Medical Research Center for Children's Health

мл. науч. сотр. Центра профилактической педиатрии, врач-диетолог ФГАУ «НМИЦ здоровья детей»

sm27@yandex.ruhttps://orcid.org/0000-0002-6701-3872GalimovaAlbina A.ГалимоваАльбина Альбертовна
Russian Federation

Res. Assist., National Medical Research Center for Children's Health

мл. науч. сотр. отд. профилактической педиатрии, врач-аллерголог ФГАУ «НМИЦ здоровья детей»

albina86@yandex.ruhttps://orcid.org/0000-0002-8172-571057193925434ChumbadzeTamara R.ЧумбадзеТамара Робертовна
Russian Federation

Cand. Sci. (Med.), National Medical Research Center for Children's Health

канд. мед. наук, ст. науч. сотр. отд. профилактической педиатрии ФГАУ «НМИЦ здоровья детей»

tamararob@rambler.ruhttps://orcid.org/0000-0001-6469-0766LebedevaAyina M.ЛебедеваАйина Михайловна
Russian Federation

laboratory assistant, National Medical Research Center for Children's Health, Federal Research Center of Nutrition, Biotechnology and Food Safety

лаборант отд. профилактической педиатрии ФГАУ «НМИЦ здоровья детей», аспирант ФГБУН «ФИЦ питания и биотехнологии»

sm27@yandex.ruNational Medical Research Center for Children's HealthФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииLomonosov Moscow State UniversityФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»Endocrinology Research CentreФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава РоссииFederal Research Center of Nutrition, Biotechnology and Food SafetyФГБУН «Федеральный исследовательский центр питания, биотехнологии и безопасности пищи»3007202221331382907202229072022Copyright ©; 2022, Consilium MedicumCopyright ©; 2022, ООО "Консилиум Медикум"2022Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://pediatria.orscience.ru/2658-6630/article/view/109545

The micronutrient status plays a key role for adequate immune response, including in diseases caused by respiratory viruses. Numerous studies conducted since the beginning of the COVID-19 pandemic, examining the impact of micronutrient availability, have shown their importance in the prevention of this disease. The largest number of publications is devoted to vitamin D. As a result, in less than two years, 17 meta-analyses and analytical reviews were published on the role of vitamin D and the availability of this micronutrient in various population groups in reducing the incidence, incidence of severe forms of COVID-19 and mortality. This review summarizes the results of published meta-analyses and systematic reviews. The analysis of literature data confirms that vitamin D has the highest evidence base as a micronutrient that reduces the risk of disease and the occurrence of severe forms of COVID-19. It also provides up-to-date recommendations on vitamin D supplementation for adult and pediatric patients.

Роль микронутриентного статуса является ключевой для формирования адекватного иммунного ответа, в том числе при заболеваниях, вызванных респираторными вирусами. Многочисленные исследования, проведенные с начала пандемии COVID-19, изучающие влияние обеспеченности микронутриентами, показали их значение в профилактике этого заболевания. Наибольшее количество публикаций посвящено витамину D, в результате менее чем за 2 года опубликовано 17 метаанализов и аналитических обзоров, посвященных роли витамина D и обеспеченности данным микронутриентом различных групп населения в снижении заболеваемости, частоты развития тяжелых форм COVID-19 и смертности. В обзоре в ходе анализа данных литературы подтверждается, что витамин D обладает наибольшей доказательной базой как микронутриент, снижающий риск заболевания тяжелыми формами COVID-19, а также приводятся рекомендации по дотации витамина D пациентам взрослого и детского возраста.

micronutrientsviral infectionscoronavirus diseasevitamin DCOVID-19SARS-CoV-2pandemicimmune responseмикронутриентывирусные инфекцииновая коронавирусная инфекциявитамин DCOVID-19SARS-CoV-2пандемияиммунный ответHidden Hunger: Malnutrition and the First 1,000 Days of Life: Causes, Consequences and Solutions. Hardback World Review of Nutrition and Dietetics. Ed. by B Koletzko, HK Biesalski, RE Black, 2016.Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients. 2020;12(4):1181. DOI:10.3390/nu12041181Фисенко А.П., Макарова С.Г. Обеспеченность микронутриентами, иммунный ответ, COVID-19. Российский педиатрический журнал. 2020;23(3):183-90 [Fisenko AP, Makarova SG. Micronutrients availability, immune response, and COVID-19. Russian Pediatric Journal. 2020;23(3):183-90 (in Russian)]. DOI:10.18821/1560-9561-2020-23-3-183-190Calder P. Conferenceon ‘Transforming the nutrition landscape in Africa’. Plenary Session 1: Feeding the immune system. Proc Nutr Soc. 2013;72:299-309.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;12:236. DOI:10.3390/nu12010236Wishart K. Increased micronutrient requirements during physiologically demanding situations: Review of the current evidence. Vitamin Miner. 2017;6:1-16.Carr AC, Shaw GM, Fowler AA., Natarajan R. Ascorbate-dependent vasopressor synthesis: а rationale for vitamin C administration in severe sepsis and septic shock? Crit Care. 2015;19:418.Gröber U, Holick MF. The coronavirus disease (COVID-19) – а supportive approach with selected micronutrients. Int J Vitam Nutr Res. 2022;92(1):13-34. DOI:10.1024/0300-9831/a000693Kumar P, Kumar M, Bedi O, et al. Role of vitamins and minerals as immunity boosters in COVID-19. Inflammopharmacology. 2021;29(4):1001-16. DOI:10.1007/s10787-021-00826-7Singh V. Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease? Curr Nutr Rep. 2020;9(3):202-9. DOI:10.1007/s13668-020-00330-4Pedrosa LFC, Barros ANAB, Leite-Lais L. Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk and clinical outcomes of COVID-19: A narrative review. Clin Nutr ESPEN. 2022;47:9-27. DOI:10.1016/j.clnesp.2021.11.003Torshin IY, Gromova OA, Chuchalin AG. Computational systematics of nutritional support of vaccination against viral and bacterial pathogens as prolegomena to vaccinations against COVID-19. medRxiv. 2021. DOI:10.1101/2021.09.10.21263398Khajavi A, Amirhakimi GH. The rachitic lung. Pulmonary findings in 30 infants and children with malnutritional rickets. Clin Pediatr (Phila). 1977;16(1):36-8 DOI:10.1177/000992287701600106Grant WB, Lahore H, McDonnell ShL, 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/nu12040988Ginde AA, Mansbach JM, Camargo CA Jr. 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;169:384-90. DOI:10.1001/archinternmed.2008.560Laaksi I, Ruohola JP, Tuohimaa P, et al. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86:714-7.Sabetta JR, DePetrillo P, Cipriani RJ, et al. Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults. PLoS ONE. 2010;5:e11088. DOI:10.1371/journal.pone.0011088Science M, Maguire JL, Russell ML, et al. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013;57:392-7. DOI:10.1093/cid/cit289Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: A systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5:986-1004.Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.Rejnmark L, Bislev LS, Cashman KD, et al. Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data. PLoS ONE. 2017;12:e0180512.Bergman P, Lindh Å, Björkhem-Bergman L, Lindh J. Vitamin D and respiratory tract infections: A systematic review and meta-analysis of randomized controlled trials. PLoS ONE. 2013;8:e65835.Charan J, Goyal J, Saxena D, Yadav P. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. J Pharmacol Pharmacother. 2012;3:300-3.Vuichard Gysin D, Dao D, Gysin CM, et al. Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2016;11:e0162996. DOI:10.1371/journal.pone.0162996Dancer RC, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax. 2015;70:617-24.Han JE, Jones JL, Tangpricha V, et al. High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. J Clin Transl Endocrinol. 2016;4:59-65.Xiao L, Xing C, Yang Z, et al. Vitamin D supplementation for the prevention of childhood acute respiratory infections: A systematic review of randomised controlled trials. Br J Nutr. 2015;114:1026-34.Yakoob MY, Salam RA, Khan FR, Bhutta ZA. Vitamin D supplementation for preventing infections in children under five years of age. Cochrane Database Syst Rev. 2016;11:CD008824.Das RR, Singh M, Naik SS. Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia. Cochrane Database Syst Rev. 2018;7:CD011597.Yamshchikov AV, Desai NS, Blumberg HM, et al. Vitamin D for treatment and prevention of infectious diseases: A systematic review of randomized controlled trials. Endocr Pract. 2009;15:438-49.Jolliffe DA, Camargo CA Jr, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021;9(5):276-92. DOI:10.1016/S2213-8587(21)00051-6Slominski AT, Slominski RM, Goepfert PA, et al. Reply to Jakovac and to Rocha et al.: Can vitamin D prevent or manage COVID-19 illness? Am J Physiol Endocrinol Metab. 2020;319(2):E455-7. DOI:10.1152/ajpendo.00348.2020Wimalawansa SJ. Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel). 2019;8(2):30. DOI:10.3390/biology8020030Ahmed A, Siman-Tov G, Hall G, et al. Human Antimicrobial Peptides as Therapeutics for Viral Infections. Viruses. 2019;11(8):704. DOI:10.3390/v11080704Slominski RM, Stefan J, Athar M, et al. COVID-19 and Vitamin D: A lesson from the skin. Exp Dermatol. 2020;29(2):885-90. DOI:10.1111/exd.14170Rhodes JM, Subramanian S, Laird E, Kenny RA. Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity. Aliment Pharmacol Ther. 2020;51(12):1434-7. DOI:10.1111/apt.15777Rao Z, Chen X, Wu J, et al. Vitamin D receptor inhibits NLRP3 activation by impeding Its BRCC3-mediated deubiquitination. Front Immunol. 2019;10:2783. DOI:10.3389/fimmu.2019.02783Xu J, Yang J, Chen J, et al. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep. 2017;16(5):7432-8. DOI:10.3892/mmr.2017.7546Kaharan S, Katkat F. Impact of serum 25(OH) vitamin D level on mortality in patients with COVID-19 in Turkey. J Nutr Health Aging. 2020;5:1-8. DOI:10.1007/s12603-020-1479-0Chiu S-K, Tsai K-W, Wu C-C, et al. Putative Role of Vitamin D for COVID-19 Vaccination. Int J Mol Sci. 2021;22:8988. DOI:10.3390/ijms22168988Maghbooli Z, Ali Sahraian M, 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.Kaufman HW, Niles JK, Kroll MH, et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020;15(9):e0239252.Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020;13(10):1373-80. DOI:10.1016/j.jiph.2020.06.021Panfili FM, Roversi M, D'Argenio P, et al. Possible role of vitamin D in Covid-19 infection in pediatric population. J Endocrinol Invest. 2021;44(1):27-35. DOI:10.1007/s40618-020-01327-0Bassatne A, Basbous M, Chakhtoura M, et al. The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism. 2021;119:154753. DOI:10.1016/j.metabol.2021.154753Teshome A, Adane A, Girma B, Mekonnen ZA. The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis. Front Public Health. 2021;9:624559. DOI:10.3389/fpubh.2021.624559Shah K, Saxena D, Mavalankar D. Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis. QJM. 2021;114(3):175-81. DOI:10.1093/qjmed/hcab009Borsche L, Glauner B, von Mendel J. COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients. 2021;13(10):3596. DOI:10.3390/nu13103596Szarpak L, Rafique Z, Gasecka A, et al. A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J. 2021;28(5):647-54. DOI:10.5603/CJ.a2021.0072Ghasemian R, Shamshirian A, Heydari K, et al. The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis. Int J Clin Pract. 2021;75(11):e14675. DOI:10.1111/ijcp.14675Petrelli F, Luciani A, Perego G, et al. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol. 2021;211:105883. DOI:10.1016/j.jsbmb.2021.105883Kaya MO, Pamukçu E, Yakar B. The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies. Epidemiol Health. 2021;43:e2021074. DOI:10.4178/epih.e2021074Crafa A, Cannarella R, Condorelli RA, et al. Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis. EClinicalMedicine. 2021;37:100967. DOI:10.1016/j.eclinm.2021.100967Akbar MR, Wibowo A, Pranata R, Setiabudiawan B. Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis. Front Nutr. 2021;8:660420. DOI:10.3389/fnut.2021.660420Corrao S, Mallaci Bocchio R, Lo Monaco M, et al. Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc. Nutrients. 2021;13(4):1261. DOI:10.3390/nu13041261Liu N, Sun J, Wang X, et al. Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis. Int J Infect Dis. 2021;104:58-64. DOI:10.1016/j.ijid.2020.12.077Ebrahimzadeh A, Mohseni S, Narimani B, et al. Association between vitamin D status and risk of covid-19 in-hospital mortality: A systematic review and meta-analysis of observational studies. Crit Rev Food Sci Nutr. 2021;9:1-11. DOI:10.1080/10408398.2021.2012419Pereira M, Dantas Damascena A, Galvão Azevedo LM, et al. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022;62(5):1308-16. DOI:10.1080/10408398.2020.1841090Wang Z, Joshi A, Leopold K, et al. Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis. Clin Endocrinol (Oxf). 2022;96(3):281-7. DOI:10.1111/cen.14540Pal R, Banerjee M, Bhadada SK, et al. Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest. 2022;45(1):53-68. DOI:10.1007/s40618-021-01614-4Varikasuvu SR, Thangappazham B, Vykunta A, et al. COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials. Expert Rev Anti Infect Ther. 2022;3:1-7. DOI:10.1080/14787210.2022.2035217Feketea G, Vlacha V, Bocsan IC, et al. Vitamin D in Corona Virus Disease 2019 (COVID-19) Related Multisystem Inflammatory Syndrome in Children (MIS-C). Front Immunol. 2021;12:648546. DOI:10.3389/fimmu.2021.648546Национальная программа «Недостаточность витамина D у детей и подростков Российской Федерации: современные подходы к коррекции». Союз педиатров России. М.: ПедиатрЪ, 2021 [Natsional'naia programma “Nedostatochnost' vitamina D u detei i podrostkov Rossiiskoi Federatsii: sovremennye podkhody k korrektsii”. Soiuz pediatrov Rossii. Moscow: Pediatr, 2021 (in Russian)].