Effect of Adjunctive Vitamin D Therapy on COVID-19 Mortality : An Evidence-Based Case Report
DOI:
https://doi.org/10.31004/joecy.v6i1.8903Keywords:
COVID-19, vitamin D, mortality, adjunctive therapyAbstract
Introduction: Vitamin D plays an essential role in immune modulation by enhancing antimicrobial peptide production (cathelicidin, defensin), suppressing proinflammatory cytokines (IL-6, TNF-α), and increasing anti-inflammatory cytokines (IL-10). These mechanisms may help reduce cytokine storm risk, a major cause of COVID-19 mortality. Observational studies have shown that low 25(OH)D levels are associated with increased disease severity and mortality, yet evidence from randomized controlled trials (RCTs) and meta-analyses remains inconsistent.
Methods: A systematic literature review was performed using PubMed, Scopus, and EBSCO databases. Eligible studies included RCTs, systematic reviews, and meta-analyses comparing standard COVID-19 therapy with or without vitamin D supplementation and reporting mortality outcomes. All selected studies were critically appraised for validity, importance, and applicability using the Centre for Evidence-Based Medicine (CEBM) tools.
Results: From 245 identified articles, six met inclusion criteria (one RCT and five systematic reviews/meta-analyses). Most reported a trend of lower mortality in the vitamin D group, though not statistically significant. One meta-analysis showed a 55% mortality risk reduction (OR = 0.45; 95% CI 0.24–0.86; p = 0.02) but with high heterogeneity (I² = 66.96%). Differences in dosage, formulation, baseline vitamin D levels, and disease severity likely contributed to inconsistent outcomes.
Conclusion: Vitamin D supplementation as adjunctive therapy shows no potential in reducing mortality among COVID-19 patients. Routine administration is not recommended; further large-scale studies with standardized doses and focus on vitamin D deficient subgroups are necessary to clarify its clinical benefits.
References
Dhama K, Khan S, Tiwari R, et al. Coronavirus Disease 2019–COVID-19. Clin Microbiol Rev. 2020;33(4). doi:https://doi.org/10.1128/cmr.00028-20
Kemenkes. Rencana Operasi Penanggulangan COVID-19 Bidang Kehehatan Di Indonesia.; 2020.
Surendra H, Elyazar IR, Djaafara BA, et al. Clinical characteristics and mortality associated with COVID-19 in Jakarta, Indonesia: A hospital-based retrospective cohort study. Lancet Reg Health West Pac. 2021;9. doi:10.1016/j.lanwpc.2021.100108
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. Evidence-based Complementary and Alternative Medicine.Hindawi Limited. 2018;2018. doi:10.1155/2018/5813095
Balla M, Merugu GP, Konala VM, et al. Back to basics: review on vitamin D and respiratory viral infections including COVID-19. J Community Hosp Intern Med Perspect. 2020;10(6):529-536. doi:10.1080/20009666.2020.1811074
Wei R, Christakos S. Mechanisms underlying the regulation of innate and adaptive immunity by vitamin D. Nutrients.MDPI AG. 2015;7(10):8251-8260. doi:10.3390/nu7105392
Angelidi AM, Belanger MJ, Lorinsky MK, et al. Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients. Mayo Clin Proc. 2021;96(4):875-886. doi:10.1016/j.mayocp.2021.01.001
Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open. 2020;3(9). doi:10.1001/jamanetworkopen.2020.19722
Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020;15(9 September 2020). doi:10.1371/journal.pone.0239252
De Niet S, Trémège M, Coffiner M, et al. Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2022;14(15). doi:10.3390/nu14153048
Caliman-Sturdza OA, Gheorghita RE, Soldanescu I. Vitamin D and COVID-19: Clinical Evidence and Immunological Insights. Life.Multidisciplinary Digital Publishing Institute (MDPI). 2025;15(5). doi:10.3390/life15050733
Ramirez-Sandoval JC, Castillos-Ávalos VJ, Paz-Cortés A, et al. Very Low Vitamin D Levels are a Strong Independent Predictor of Mortality in Hospitalized Patients with Severe COVID-19: Hypovitaminosis D and COVID-19 mortality. Arch Med Res. 2022;53(2):215-222. doi:10.1016/j.arcmed.2021.09.006
Kümmel LS, Krumbein H, Fragkou PC, et al. Vitamin D supplementation for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Front Immunol. 2022;13. doi:10.3389/fimmu.2022.1023903
Murai IH, Fernandes AL, Antonangelo L, Gualano B, Pereira RMR. Effect of a single high-dose vitamin D3 on the length of hospital stay of severely 25-hydroxyvita-min D-deficient patients with COVID-19. Clinics. 2021;76. doi:10.6061/clinics/2021/e3549
Tentolouris N, Samakidou G, Eleftheriadou I, Tentolouris A, Jude EB. The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression. Diabetes Metab Res Rev. 2022;38(4). doi:10.1002/dmrr.3517
Mirghani H, Begum S. Vitamin D supplementations and mortality among patients with moderate/severe COVID-19: A meta-analysis of randomized controlled trials. Journal of Research in Medical Sciences.Wolters Kluwer Medknow Publications. 2024;29(1). doi:10.4103/jrms.jrms_591_23
Sartini M, Del Puente F, Carbone A, et al. The Effect of Vitamin D Supplementation Post COVID-19 Infection and Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients .Multidisciplinary Digital Publishing Institute (MDPI). 2024;16(22). doi:10.3390/nu16223794
Rawat D, Roy A, Maitra S, Shankar V, Khanna P, Baidya DK. “Vitamin D supplementation and COVID-19 treatment: A systematic review and meta-analysis.” Diabetes and Metabolic Syndrome: Clinical Research and Reviews.Elsevier Ltd. 2021;15(4). doi:10.1016/j.dsx.2021.102189
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