The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), a type of coronavirus that causes the condition known as coronavirus disease, was first reported in Wuhan, China in 2019. It commonly affects the respiratory system and is known to produce, in some cases, pneumonia like symptoms, and even death. However, 25 hydroxyvitamin D commonly known as vitamin D, is, when in its hormonal form, involved in many processes throughout the body, including bone health and immune function. Several studies have linked vitamin D to increased resistance to infection, but the link between vitamin D levels and COVID-19 infection, severity and mortality is yet to be fully ascertained. Several studies have linked vitamin D serum levels and deficiency to differing levels of COVID-19 outcome. This review seeks to investigate these claims made in these studies to help add to the body of knowledge and come to a greater understanding of the link between vitamin D and COVID-19 infection.
Citation: Marcus Martin, Reinand Thompson, Nikhil Tirupathi. Does vitamin D level have effect on COVID-19 outcomes?[J]. AIMS Medical Science, 2023, 10(2): 141-150. doi: 10.3934/medsci.2023012
The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), a type of coronavirus that causes the condition known as coronavirus disease, was first reported in Wuhan, China in 2019. It commonly affects the respiratory system and is known to produce, in some cases, pneumonia like symptoms, and even death. However, 25 hydroxyvitamin D commonly known as vitamin D, is, when in its hormonal form, involved in many processes throughout the body, including bone health and immune function. Several studies have linked vitamin D to increased resistance to infection, but the link between vitamin D levels and COVID-19 infection, severity and mortality is yet to be fully ascertained. Several studies have linked vitamin D serum levels and deficiency to differing levels of COVID-19 outcome. This review seeks to investigate these claims made in these studies to help add to the body of knowledge and come to a greater understanding of the link between vitamin D and COVID-19 infection.
| [1] |
To KK, Sridhar S, Chiu KH, et al. (2021) Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic. Emerg Microbes Infect 10: 507-535. https://doi.org/10.1080/22221751.2021.1898291 
|
| [2] |
Rothan HA, Byrareddy SN (2020) The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 109: 102433. https://doi.org/10.1016/j.jaut.2020.102433
|
| [3] |
Li Q, Guan X, Wu P, et al. (2020) Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 382: 1199-1207. https://doi.org/10.1056/NEJMoa2001316
|
| [4] |
Wang W, Tang J, Wei F (2020) Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol 92: 441-447. https://doi.org/10.1002/jmv.25689
|
| [5] |
Huang C, Wang Y, Li X, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506. https://doi.org/10.1016/S0140-6736(20)30183-5
|
| [6] |
Singhal T (2020) A review of Coronavirus disease-2019 (COVID-19). Indian J Pediatr 87: 281-286. https://doi.org/10.1007/s12098-020-03263-6
|
| [7] |
Shang J, Wan Y, Liu C, et al. (2020) Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry. PLoS Pathog 16: e1008392. https://doi.org/10.1371/journal.ppat.1008392
|
| [8] |
Angeletti S, Benvenuto D, Bianchi M, et al. (2020) COVID-2019: the role of the nsp2 and nsp3 in its pathogenesis. J Med Virol 92: 584-588. https://doi.org/10.1002/jmv.25719
|
| [9] |
Cui J, Li F, Shi ZL (2019) Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17: 181-192. https://doi.org/10.1038/s41579-018-0118-9
|
| [10] |
Channappanavar R, Perlman S (2017) Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 39: 529-539. https://doi.org/10.1007/s00281-017-0629-x
|
| [11] |
Channappanavar R, Fehr AR, Vijay R, et al. (2016) Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe 19: 181-193. https://doi.org/10.1016/j.chom.2016.01.007
|
| [12] |
Chu CM, Poon LL, Cheng VC, et al. (2004) Initial viral load and the outcomes of SARS. CMAJ 171: 1349-1352. https://doi.org/10.1503/cmaj.1040398
|
| [13] |
Kohlmeier JE, Cookenham T, Roberts AD, et al. (2010) Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge. Immunity 33: 96-105. https://doi.org/10.1016/j.immuni.2010.06.016
|
| [14] |
Schuster I (2011) Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta 1814: 186-199. https://doi.org/10.1016/j.bbapap.2010.06.022
|
| [15] |
Haussler MR, Haussler CA, Bartik L, et al. (2008) Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev 66: S98-S112. https://doi.org/10.1111/j.1753-4887.2008.00093.x
|
| [16] |
Jurutka PW, Bartik L, Whitfield GK, et al. (2007) Vitamin D receptor: key roles in bone mineral pathophysiology, molecular mechanism of action, and novel nutritional ligands. J Bone Miner Res 22: V2-V10. https://doi.org/10.1359/jbmr.07s216
|
| [17] |
Bell NH, Shary J, Shaw S, et al. (1985) Hypercalcemia associated with increased circulating 1, 25 dihydroxyvitamin D in a patient with pulmonary tuberculosis. Calcif Tissue Int 37: 588-591.
|
| [18] | Rook GA, Steele J, Fraher L, et al. (1986) Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57: 159-163. |
| [19] |
Liu PT, Stenger S, Li H, et al. (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311: 1770-1773. https://doi.org/10.1126/science.1123933
|
| [20] | Brennan A, Katz DR, Nunn JD, et al. (1987) Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology 61: 457-461. |
| [21] | Nunn JD, Katz DR, Barker S, et al. (1986) Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3. Immunology 59: 479-484. |
| [22] |
Rondanelli M, Miccono A, Lamburghini S, et al. (2018) 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: 5813095. https://doi.org/10.1155/2018/5813095
|
| [23] |
Ali N (2020) Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health 13: 1373-1380. https://doi.org/10.1016/j.jiph.2020.06.021
|
| [24] |
Chen H, Lu R, Zhang YG, et al. (2018) Vitamin D receptor deletion leads to the destruction of tight and adherens junctions in lungs. Tissue Barriers 6: 1-13. https://doi.org/10.1080/21688370.2018.1540904
|
| [25] |
Gniadecki R, Gajkowska B, Hansen M (1997) 1,25-dihydroxyvitamin D3 stimulates the assembly of adherens junctions in keratinocytes: involvement of protein kinase C. Endocrinology 138: 2241-2248. https://doi.org/10.1210/endo.138.6.5156
|
| [26] |
Clairmont A, Tessman D, Stock A, et al. (1996) Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear vitamin D receptor. Carcinogenesis 17: 1389-1391. https://doi.org/10.1093/carcin/17.6.1389
|
| [27] |
Currie SM, Findlay EG, McHugh BJ, et al. (2013) The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus. PloS One 8: e73659. https://doi.org/10.1371/journal.pone.0073659
|
| [28] |
Hansdottir S, Monick MM, Hinde SL, et al. (2008) Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 181: 7090-7099. https://doi.org/10.4049/jimmunol.181.10.7090
|
| [29] | Lemire JM, Archer DC, Beck L, et al. (1995) Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 125: 1704S-1708S. https://doi.org/10.1093/jn/125.suppl_6.1704S |
| [30] |
Boonstra A, Barrat FJ, Crain C, et al. (2001) 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167: 4974-4980. https://doi.org/10.4049/jimmunol.167.9.4974
|
| [31] |
Kaiko GE, Horvat JC, Beagley KW, et al. (2008) Immunological decision-making: how does the immune system decide to mount a helper T-cell response?. Immunology 123: 326-338. https://doi.org/10.1111/j.1365-2567.2007.02719.x
|
| [32] |
Sabetta JR, DePetrillo P, Cipriani RJ, et al. (2010) Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PloS One 5: e11088. https://doi.org/10.1371/journal.pone.0011088
|
| [33] |
Science M, Maguire JL, Russell ML, et al. (2013) Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis 57: 392-397. https://doi.org/10.1093/cid/cit289
|
| [34] |
Autier P, Boniol M, Pizot C, et al. (2014) Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2: 76-89. https://doi.org/10.1016/S2213-8587(13)70165-7
|
| [35] |
Major JM, Graubard BI, Dodd KW, et al. (2013) Variability and reproducibility of circulating vitamin D in a nationwide U.S. population. J Clin Endocrinol Metab 98: 97-104. https://doi.org/10.1210/jc.2012-2643
|
| [36] | Terushkin V, Bender A, Psaty EL, et al. (2010) Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. J Am Acad Dermatol 62: 929.e1-929.e9. https://doi.org/10.1016/j.jaad.2009.07.028 |
| [37] |
Thuesen B, Husemoen L, Fenger M, et al. (2012) Determinants of vitamin D status in a general population of Danish adults. Bone 50: 605-610. https://doi.org/10.1016/j.bone.2011.12.016
|
| [38] |
Pourshahidi LK (2015) Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc 74: 115-124. https://doi.org/10.1017/S0029665114001578
|
| [39] |
Singh R, Rathore SS, Khan H, et al. (2022) Association of obesity with COVID-19 severity and mortality: an updated systemic review, meta-analysis, and meta-regression. Front Endocrinol 13: 780872. https://doi.org/10.3389/fendo.2022.780872
|
| [40] |
Huang Y, Lu Y, Huang YM, et al. (2020) Obesity in patients with COVID-19: a systematic review and meta-analysis. Metabolism 113: 154378. https://doi.org/10.1016/j.metabol.2020.154378
|
| [41] |
Ames BN, Grant WB, Willett WC (2021) Does the high prevalence of vitamin D deficiency in African Americans contribute to health disparities?. Nutrients 13: 499. https://doi.org/10.3390/nu13020499
|
| [42] |
Carlberg C (2022) Vitamin D and pigmented skin. Nutrients 14: 325. https://doi.org/10.3390/nu14020325
|
| [43] |
Wierzbicka A, Oczkowicz M (2022) Sex differences in vitamin D metabolism, serum levels and action. Br J Nutr 128: 2115-2130. https://doi.org/10.1017/S0007114522000149
|
| [44] |
Meltzer DO, Best TJ, Zhang H, et al. (2020) Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open 3: e2019722. https://doi.org/10.1001/jamanetworkopen.2020.19722
|
| [45] |
Merzon E, Tworowski D, Gorohovski A, et al. (2020) Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J 287: 3693-3702. https://doi.org/10.1111/febs.15495
|
| [46] | Mendy A, Apewokin S, Wells AA, et al. (2020) Factors associated with hospitalization and disease severity in a racially and ethnically diverse population of COVID-19 patients. medRxiv . https://doi.org/10.1101/2020.06.25.20137323 |
| [47] |
Kotur N, Skakic A, Klaassen K, et al. (2021) Association of vitamin D, Zinc and Selenium related genetic variants with COVID-19 disease severity. Front Nutr 8: 689419. https://doi.org/10.3389/fnut.2021.689419
|
| [48] |
Carpagnano GE, Di Lecce V, Quaranta VN, et al. (2021) Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest 44: 765-771. https://doi.org/10.1007/s40618-020-01370-x
|
| [49] |
Fasano A, Cereda E, Barichella M, et al. (2020) COVID-19 in Parkinson's disease patients living in Lombardy, Italy. Mov Disord 35: 1089-1093. https://doi.org/10.1002/mds.28176
|
| [50] |
Szeto B, Zucker JE, LaSota ED, et al. (2021) Vitamin D status and COVID-19 clinical outcomes in hospitalized patients. Endocr Res 46: 66-73. https://doi.org/10.1080/07435800.2020.1867162
|
| [51] |
Dror AA, Morozov N, Daoud A, et al. (2022) Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness. PloS One 17: e0263069. https://doi.org/10.1371/journal.pone.0263069
|
| [52] |
Hastie CE, Mackay DF, Ho F, et al. (2020) Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr 14: 561-565. https://doi.org/10.1016/j.dsx.2020.04.050
|
| [53] |
Bae M, Kim H (2020) Mini-review on the roles of vitamin C, vitamin D, and Selenium in the immune system against COVID-19. Molecules 25: 5346. https://doi.org/10.3390/molecules25225346
|
| [54] |
Lips P, Cashman KD, Lamberg-Allardt C, et al. (2019) Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur J Endocrinol 180: P23-P54. https://doi.org/10.1530/EJE-18-0736
|
| [55] | Alipio M (2020) Vitamin D supplementation could possibly improve clinical outcomes of patients infected with coronavirus-2019 (COVID-2019). Available at SSRN 3571484 |
| [56] |
Tan CW, Ho LP, Kalimuddin S, et al. (2020) Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19). Nutrition 79–80: 111017. https://doi.org/10.1016/j.nut.2020.111017
|
| [57] |
Darling AL, Ahmadi KR, Ward KA, et al. (2020) Vitamin D concentration, body mass index, ethnicity and SARS-CoV-2/COVID-19: initial analysis of the first- reported UK Biobank Cohort positive cases (n 1474) compared with negative controls (n 4643). P Nutr Soc 80: E17. https://doi.org/10.1017/S0029665121000185
|
| [58] |
Vassiliou AG, Jahaj E, Pratikaki M, et al. (2020) Low 25-Hydroxyvitamin D levels on admission to the intensive care unit may predispose COVID-19 pneumonia patients to a higher 28-day mortality risk: a pilot study on a Greek ICU cohort. Nutrients 12: 3773. https://doi.org/10.3390/nu12123773
|
Marcus Martin, Reinand Thompson, Nikhil Tirupathi. Does vitamin D level have effect on COVID-19 outcomes?[J]. AIMS Medical Science, 2023, 10(2): 141-150. doi: 10.3934/medsci.2023012
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