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DOI: 10.1055/s-0041-1730084
Immunomodulatory Effects of Vitamin D and Vitamin C to Improve Immunity in COVID-19 Patients
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection causes life-threatening respiratory illness, which has caused significant mortality and morbidity around the globe. Coronavirus disease 2019 (COVID-19) causes mild respiratory illness in most infected individuals; however, in some patients it may progress to sepsis, acute respiratory distress syndrome (ARDS), cytokine release syndrome (CRS), and multiorgan dysfunction (MODS), which results in intensive care unit (ICU) admissions and increased fatalities. Recent evidence shows that most of these comorbidities associated with COVID-19 infection are associated with dysregulation of the host immune response. Vitamins C and D have been shown to regulate immune response by decreasing the proinflammatory cytokine release from immune cells and inducing proliferation of other immune cells to robustly fight infection. This review critically evaluates the current literature on vitamins C and D in modulating an immune response in different diseases and their potential therapeutic effects in preventing complications in COVID-19 infection.
Publication History
Article published online:
12 May 2021
© 2021. Nitte (Deemed to be University). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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References
- 1 Felsenstein S, Herbert JA, McNamara PS. Hedrich CM. COVID-19: immunology and treatment options. Clin Immunol 2020; 215: 108448
- 2 Vabret N, Britton GJ, Gruber C. et al Sinai Immunology Review Project. Immunology of COVID-19: current state of the science. Immunity 2020; 52 (06) 910-941
- 3 Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). Treasure Island, FL: StatPearls 2020
- 4 Goldsmith JR. Vitamin D as an immunomodulator: risks with deficiencies and benefits of supplementation. Healthcare (Basel) 2015; 3 (02) 219-232
- 5 Myszka M, Klinger M. The immunomodulatory role of Vitamin D. Postepy Hig Med Dosw 2014; 68: 865-878
- 6 Sassi F, Tamone C, D’Amelio P, Vitamin D. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients 2018; 10 (11) E1656
- 7 Mousavi S, Bereswill S, Heimesaat MM. Immunomodulatory and antimicrobial effects of vitamin C. Eur J Microbiol Immunol (Bp) 2019; 9 (03) 73-79
- 8 Carr AC, Maggini S. Vitamin C and immune function. Nutrients 2017; 9 (11) E1211
- 9 Hemilä H, Chalker E, Vitamin C. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients 2019; 11 (04) E708
- 10 Johnston CS, Beezhold BL, Mostow B, Swan PD. Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in nonsmoking adults. J Nutr 2007; 137 (07) 1757-1762
- 11 Johnston CS, Corte C, Swan PD. Marginal vitamin C status is associated with reduced fat oxidation during submaximal exercise in young adults. Nutr Metab (Lond) 2006; 3: 35
- 12 Kivirikko KI, Myllylä R, Pihlajaniemi T. Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. FASEB J 1989; 3 (05) 1609-1617
- 13 Ströhle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection—ascorbic acid and calciferol: part 1, general overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets 2011; 10 (01) 54-63
- 14 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357 (03) 266-281
- 15 Pike JW, Christakos S. Biology and mechanisms of action of the Vitamin D hormone. Endocrinol Metab Clin North Am 2017; 46 (04) 815-843
- 16 Bivona G, Agnello L, Ciaccio M. Vitamin D and immunomodulation: is it time to change the reference values?. Ann Clin Lab Sci 2017; 47 (04) 508-510
- 17 Rondanelli M, Miccono A, Lamburghini S. 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
- 18 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 (01) 96-108
- 19 Chen Y, Leng K, Lu Y. et al Epidemiological features and time-series analysis of influenza incidence in urban and rural areas of Shenyang, China, 2010-2018. Epidemiol Infect 2020; 148: e29
- 20 Kast JI, McFarlane AJ, Głobińska A. et al Respiratory syncytial virus infection influences tight junction integrity. Clin Exp Immunol 2017; 190 (03) 351-359
- 21 Rossi GA, Fanous H, Colin AA. Viral strategies predisposing to respiratory bacterial superinfections. Pediatr Pulmonol 2020; 55 (04) 1061-1073
- 22 Adams JS, Ren S, Liu PT. et al Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 2009; 182 (07) 4289-4295
- 23 Laaksi I. Vitamin D and respiratory infection in adults. Proc Nutr Soc 2012; 71 (01) 90-97
- 24 Liu PT, Stenger S, Li H. et al Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311 (5768) 1770-1773
- 25 Herr C, Shaykhiev R, Bals R. The role of cathelicidin and defensins in pulmonary inflammatory diseases. Expert Opin Biol Ther 2007; 7 (09) 1449-1461
- 26 Agier J, Efenberger M, Brzezińska-Błaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol 2015; 40 (02) 225-235
- 27 Barlow PG, Svoboda P, Mackellar A. et al Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS One 2011; 6 (10) e25333
- 28 Zhao Y, Ran Z, Jiang Q. 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) E3562
- 29 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
- 30 Sharifi A, Vahedi H, Nedjat S, Rafiei H, Hosseinzadeh-Attar MJ. Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebo-controlled trial. APMIS 2019; 127 (10) 681-687
- 31 Cantorna MT, Snyder L, Lin YD, Yang L. Vitamin D and 1,25(OH) 2D regulation of T cells. Nutrients 2015; 7 (04) 3011-3021
- 32 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 (01) E236
- 33 Jeffery LE, Burke F, Mura M. et al 1,25-dihydroxyvitamin D3 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 (09) 5458-5467
- 34 Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J 1996; 10 (07) 709-720
- 35 Chen Y, Luo G, Yuan J. et al Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages. Mediators Inflamm 2014; 2014: 426740
- 36 Härtel C, Strunk T, Bucsky P, Schultz C. Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes. Cytokine 2004; 27 (4-5) 101-106
- 37 Cárcamo JM, Bórquez-Ojeda O, Golde DW. Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways. Blood 2002; 99 (09) 3205-3212
- 38 Maeng HG, Lim H, Jeong YJ. et al Vitamin C enters mouse T cells as dehydroascorbic acid in vitro and does not recapitulate in vivo vitamin C effects. Immunobiology 2009; 214 (04) 311-320
- 39 Tanaka M, Muto N, Gohda E, Yamamoto I. Enhancement by ascorbic acid 2-glucoside or repeated additions of ascorbate of mitogen-induced IgM and IgG productions by human peripheral blood lymphocytes. Jpn J Pharmacol 1994; 66 (04) 451-456
- 40 Delgado-Roche L, Mesta F. Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res 2020; 51 (05) 384-387
- 41 Kratzer E, Tian Y, Sarich N. et al Oxidative stress contributes to lung injury and barrier dysfunction via microtubule destabilization. Am J Respir Cell Mol Biol 2012; 47 (05) 688-697
- 42 Fisher BJ, Kraskauskas D, Martin EJ. et al Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol 2012; 303 (01) L20-L32
- 43 Lang JD, McArdle PJ, O’Reilly PJ, Matalon S. Oxidant-antioxidant balance in acute lung injury. Chest 2002; 122 (06) ,Suppl) 314S-320S
- 44 Bharara A, Grossman C, Grinnan D. et al Intravenous Vitamin C administered as adjunctive therapy for recurrent acute respiratory distress syndrome. Case Rep Crit Care 2016; 2016: 8560871
- 45 Furuya A, Uozaki M, Yamasaki H, Arakawa T, Arita M, Koyama AH. Antiviral effects of ascorbic and dehydroascorbic acids in vitro. Int J Mol Med 2008; 22 (04) 541-545
- 46 Brant EB, Angus DC. Is high-dose vitamin C beneficial for patients with sepsis. ? JAMA 2019; 322 (13) 1257-1258
- 47 Marik PE, Hooper MH. Doctor-your septic patients have scurvy!. Crit Care 2018; 22 (01) 23
- 48 Chen JY, Chang CY, Feng PH, Chu CC, So EC, Hu ML. Plasma vitamin C is lower in postherpetic neuralgia patients and administration of vitamin C reduces spontaneous pain but not brush-evoked pain. Clin J Pain 2009; 25 (07) 562-569
- 49 Fowler AA II, Truwit JD, Hite RD. et al Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. JAMA 2019; 322 (13) 1261-1270
- 50 Valero N, Mosquera J, Alcocer S, Bonilla E, Salazar J, Álvarez-Mon M. Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis. Brain Res 2015; 1622: 368-376
- 51 Li W, Maeda N, Beck MA. Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice. J Nutr 2006; 136 (10) 2611-2616
- 52 Cai Y, Li YF, Tang LP. et al A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice. Bio Med Res Int 2015; 2015: 675149
- 53 Cyprian F, Lefkou E, Varoudi K, Girardi G. Immunomodulatory effects of vitamin D in pregnancy and beyond. Front Immunol 2019; 10: 2739
- 54 Hartel C, Puzik A, Gopel W, Temming P, Bucsky P, Schultz C. Immunomodulatory effect of vitamin C on intracytoplasmic cytokine production in neonatal cord blood cells. Neonatology 2007; 91 (01) 54-60
- 55 Buffinton GD, Doe WF. Altered ascorbic acid status in the mucosa from inflammatory bowel disease patients. Free Radic Res 1995; 22 (02) 131-143
- 56 Panfili FM, Roversi M, D’Argenio P, Rossi P, Cappa M, Fintini D. Possible role of vitamin D in COVID-19 infection in pediatric population. J Endocrinol Invest 2020