Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?

Hubert Mado; Edyta Reichman-Warmusz; Damian Dudek; Oliwia Warmusz

doi:10.29333/ejgm/9762

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Hubert Mado ¹ ^* , Edyta Reichman-Warmusz ¹ , Damian Dudek ¹ , Oliwia Warmusz ¹

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¹ Department of Histology and Cell Pathology in Zabrze, Medical University of Silesia in Katowice. Jordana Street 19, 41-808 Zabrze, POLAND^* Corresponding Author

Abstract

Vitamin D, through various mechanisms, affects the immune system, resulting in antiviral effects. Recent studies have also shown that it is effective and safe in the prevention of acute respiratory infections. For this reason, in the era of Coronavirus Disease 2019 pandemic (COVID-19), it is speculated whether vitamin D may also have a positive effect in the course of COVID-19. However, the results of available studies are contradictory, although due to the safety of vitamin D, as well as the information known so far, its regular supplementation in people at risk of deficiency seems to be reasonable.

Keywords

vitamin D
coronavirus disease 2019
COVID-19
SARS-CoV-2
acute respiratory infections

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article Type: Review Article

ELECTRON J GEN MED, Volume 18, Issue 2, April 2021, Article No: em283

https://doi.org/10.29333/ejgm/9762

Publication date: 07 Mar 2021

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References

Bergman P. The link between vitamin D and COVID-19: distinguishing facts from fiction. J Intern Med. 2021 Jan;289(1):131-3. https://doi.org/10.1111/joim.13158 PMID:32652766 PMCID:PMC7405052
Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar;85(3):860-8. https://doi.org/10.1093/ajcn/85.3.860 PMID:17344510
Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011 Jun;7(6):337-45. https://doi.org/10.1038/nrendo.2010.226
Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. https://doi.org/10.1136/bmj.i6583 PMID:28202713 PMCID: PMC5310969
Bilezikian JP, Bikle D, Hewison M, Lazaretti-Castro M, Formenti AM, Gupta A, Madhavan MV, Nair N, Babalyan V, Hutchings N, Napoli N, Accili D, Binkley N, Landry DW, Giustina A. Mechanisms in Endocrinology: Vitamin D and COVID-19. Eur J Endocrinol. 2020 Nov;183(5):R133-R147. https://doi.org/10.1530/EJE-20-0665 PMID: 32755992
Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. 2015 May 29;7(6):4240-70. https://doi.org/10.3390/nu7064240 PMID:26035247 PMCID: PMC4488782
Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH, Kim JM, Jo EK. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009 Sep 17;6(3):231-43. https://doi.org/10.1016/j.chom.2009.08.004 PMID:19748465
Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005 Jul;19(9):1067-77. https://doi.org/10.1096/fj.04-3284com PMID:15985530
Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004 Sep 1;173(5):2909-12. https://doi.org/10.4049/jimmunol.173.5.2909
Campbell GR, Spector SA. Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog. 2012;8(5):e1002689. https://doi.org/10.1371/journal.ppat.1002689 PMID: 22589721 PMCID:PMC3349755.
Barlow PG, Svoboda P, Mackellar A, Nash AA, York IA, Pohl J, Davidson DJ, Donis RO. Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS One. 2011;6(10):e25333. https://doi.org/10.1371/journal.pone.0025333 PMID: 22031815 PMCID:PMC3198734
Ahmed A, Siman-Tov G, Hall G, Bhalla N, Narayanan A. Human Antimicrobial Peptides as Therapeutics for Viral Infections. Viruses. 2019 Aug 1;11(8):704. https://doi.org/10.3390/v11080704 PMID:31374901 PMCID: PMC6722670
Campbell GR, Spector SA. Autophagy induction by vitamin D inhibits both Mycobacterium tuberculosis and human immunodeficiency virus type 1. Autophagy. 2012 Oct;8(10):1523-5. https://doi.org/10.4161/auto.21154 PMID:22892387 PMCID:PMC3679232
Rook GA, Steele J, Fraher L, Barker S, Karmali R, O’Riordan J, Stanford J. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology. 1986 Jan;57(1):159-63. PMID:3002968 PMCID:PMC1453883
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, et al.. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24;311(5768):1770-3. https://doi.org/10.1126/science.1123933 PMID:16497887
Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009 Apr 1;182(7):4289-95. https://doi.org/10.4049/jimmunol.0803736 PMID:19299728 PMCID:PMC2683618
Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010 Jan 22;285(4):2227-31. https://doi.org/10.1074/jbc.C109.071225 PMID:19948723 PMCID: PMC2807280
Kim J, Yang YL, Jang SH, Jang YS. Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity. Virol J. 2018 Aug 8;15(1):124. https://doi.org/10.1186/s12985-018-1035-2 PMID:30089512 PMCID:PMC6083524
Ganz T. Hepcidin--a peptide hormone at the interface of innate immunity and iron metabolism. Curr Top Microbiol Immunol. 2006;306:183-98. https://doi.org/10.1007/3-540-29916-5_7 PMID:16909922
Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, et al. Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol. 2014 Mar;25(3):564-72. https://doi.org/10.1681/ASN.2013040355 PMID:24204002 PMCID:PMC3935584
Chan TY. Vitamin D deficiency and susceptibility to tuberculosis. Calcif Tissue Int. 2000 Jun;66(6):476-8. https://doi.org/10.1007/s002230010095 PMID:10821887
Shin DM, Yuk JM, Lee HM, Lee SH, Son JW, Harding CV, Kim JM, Modlin RL, Jo EK. Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell Microbiol. 2010 Nov;12(11):1648-65. https://doi.org/10.1111/j.1462-5822.2010.01497.x PMID:20560977 PMCID:PMC2970753
Campbell GR, Spector SA. Toll-like receptor 8 ligands activate a vitamin D mediated autophagic response that inhibits human immunodeficiency virus type 1. PLoS Pathog. 2012;8(11):e1003017. https://doi.org/10.1371/journal.ppat.1003017 PMID:23166493 PMCID:PMC3499571
Campbell GR, Spector SA. Hormonally active vitamin D3 (1alpha,25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection. J Biol Chem. 2011 May 27;286(21):18890-902. https://doi.org/10.1074/jbc.M110.206110 PMID:21454634 PMCID: PMC3099705
Teymoori-Rad M, Shokri F, Salimi V, Marashi SM. The interplay between vitamin D and viral infections. Rev Med Virol. 2019 Mar;29(2):e2032. https://doi.org/10.1002/rmv.2032 PMID:30614127
Abdel-Mohsen MA, El-Braky AA, Ghazal AAE, Shamseya MM. Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus. Medicine (Baltimore). 2018 Mar;97(12):e0172. https://doi.org/10.1097/MD.0000000000010172 PMID: 29561429 PMCID:PMC5895342
Khare D, Godbole NM, Pawar SD, Mohan V, Pandey G, et al. Calcitriol [1, 25[OH]2 D3] pre- and post-treatment suppresses inflammatory response to influenza A (H1N1) infection in human lung A549 epithelial cells. Eur J Nutr. 2013 Jun;52(4):1405-15. https://doi.org/10.1007/s00394-012-0449-7 PMID:23015061
Tian G, Liang X, Chen D, Mao X, Yu J, Zheng P, He J, Huang Z, Yu B. Vitamin D3 supplementation alleviates rotavirus infection in pigs and IPEC-J2 cells via regulating the autophagy signaling pathway. J Steroid Biochem Mol Biol. 2016 Oct;163:157-63. https://doi.org/10.1016/j.jsbmb.2016.05.004 PMID:27174720
Mushegian AA. Autophagy and vitamin D. Sci Signal. 2017 Mar 21;10(471):eaan2526. https://doi.org/10.1126/scisignal.aan2526 PMID:28325820
Uberti F, Lattuada D, Morsanuto V, Nava U, Bolis G, Vacca G, Squarzanti DF, Cisari C, Molinari C. Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways. J Clin Endocrinol Metab. 2014 Apr;99(4):1367-74. https://doi.org/10.1210/jc.2013-2103 PMID:24285680
Wang J. Beclin 1 bridges autophagy, apoptosis and differentiation. Autophagy. 2008 Oct;4(7):947-8. https://doi.org/10.4161/auto.6787 PMID:18769161
Jang W, Kim HJ, Li H, Jo KD, Lee MK, Song SH, Yang HO. 1,25-Dyhydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. Biochem Biophys Res Commun. 2014 Aug 15;451(1):142-7. https://doi.org/10.1016/j.bbrc.2014.07.081 PMID:25078626
van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):93-101. https://doi.org/10.1016/j.jsbmb.2005.06.002 PMID:16046118
Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther. 2008 Jan;324(1):23-33. https://doi.org/10.1124/jpet.107.127209 PMID:17911375
Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol. 2001 Aug 15;167(4):1945-53. https://doi.org/10.4049/jimmunol.167.4.1945 PMID:11489974
Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2011 May;241(1):260-8. https://doi.org/10.1111/j.1600-065X.2011.01018.x PMID:21488902 PMCID:PMC3077798
D’Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, Keller F, Cantù M. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients. 2020 May 9;12(5):1359. https://doi.org/10.3390/nu12051359 PMID:32397511 PMCID:PMC7285131
Rhodes JM, Subramanian S, Laird E, Griffin G, Kenny RA. Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis. J Intern Med. 2021 Jan;289(1):97-115. https://doi.org/10.1111/joim.13149 PMID:32613681 PMCID:PMC7361294
Marik PE, Kory P, Varon J. Does vitamin D status impact mortality from SARS-CoV-2 infection? Med Drug Discov. 2020 Jun;6:100041. https://doi.org/10.1016/j.medidd.2020.100041 PMID:32352080 PMCID:PMC7189189
Bernard JJ, Gallo RL, Krutmann J. Photoimmunology: how ultraviolet radiation affects the immune system. Nat Rev Immunol. 2019 Nov;19(11):688-701. https://doi.org/10.1038/s41577-019-0185-9 PMID:31213673
Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020 Oct;13(10):1373-1380. https://doi.org/10.1016/j.jiph.2020.06.021 PMID:32605780 PMCID:PMC7305922
Tan CW, Ho LP, Kalimuddin S, Cherng BPZ, Teh YE, Thien SY, Wong HM, Tern PJW, Chandran M, Chay JWM, Nagarajan C, Sultana R, Low JGH, Ng HJ. 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. 2020 Nov-Dec;79-80:111017. https://doi.org/10.1016/j.nut.2020.111017 PMID:33039952 PMCID:PMC7832811
Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. 2020 Jul;32(7):1195-8. https://doi.org/10.1007/s40520-020-01570-8 PMID:32377965 PMCID:PMC7202265
Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O’Donnell CA, Gill JM, Sattar N, Pell JP. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020 Jul-Aug;14(4):561-565. https://doi.org/10.1016/j.dsx.2020.04.050
Darling A, Ahmadi K, Ward K, Harvey N, Alves A, Dunn-Walters D, Lanham-New S, Cooper C, Blackbourn D. Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). 2020; [preprint].
Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020 Apr 2;12(4):988. https://doi.org/10.3390/nu12040988 PMID: 32252338 PMCID:PMC7231123
McCullough PJ, Lehrer DS, Amend J. Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience. J Steroid Biochem Mol Biol. 2019 May;189:228-239. https://doi.org/10.1016/j.jsbmb.2018.12.010 PMID:30611908
Malihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, Khaw KT, Camargo CA, Scragg R. Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial. Am J Clin Nutr. 2019 Jun 1;109(6):1578-87. https://doi.org/10.1093/ajcn/nqy378 PMID:31005969
Amir E, Simmons CE, Freedman OC, Dranitsaris G, Cole DE, Vieth R, Ooi WS, Clemons M. A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases. Cancer. 2010 Jan 15;116(2):284-91. https://doi.org/10.1002/cncr.24749 PMID:19918922
Charoenngam N, Shirvani A, Kalajian TA, Song A, Holick MF. The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study. Anticancer Res. 2020 Jan;40(1):551-556. https://doi.org/10.21873/anticanres.13984 PMID:31892611

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Vancouver

Mado H, Reichman-Warmusz E, Dudek D, Warmusz O. Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?. ELECTRON J GEN MED. 2021;18(2):em283. https://doi.org/10.29333/ejgm/9762

APA

Mado, H., Reichman-Warmusz, E., Dudek, D., & Warmusz, O. (2021). Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?. Electronic Journal of General Medicine, 18(2), em283. https://doi.org/10.29333/ejgm/9762

AMA

Mado H, Reichman-Warmusz E, Dudek D, Warmusz O. Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?. ELECTRON J GEN MED. 2021;18(2), em283. https://doi.org/10.29333/ejgm/9762

Chicago

Mado, Hubert, Edyta Reichman-Warmusz, Damian Dudek, and Oliwia Warmusz. "Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?". Electronic Journal of General Medicine 2021 18 no. 2 (2021): em283. https://doi.org/10.29333/ejgm/9762

Harvard

Mado, H., Reichman-Warmusz, E., Dudek, D., and Warmusz, O. (2021). Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?. Electronic Journal of General Medicine, 18(2), em283. https://doi.org/10.29333/ejgm/9762

MLA

Mado, Hubert et al. "Is Vitamin D Supplementation Protective against Coronavirus Disease 2019 (COVID-19)?". Electronic Journal of General Medicine, vol. 18, no. 2, 2021, em283. https://doi.org/10.29333/ejgm/9762