Association Between Vitamin D and COVID-19–Related Outcomes: An Umbrella Review of Meta-Analyses

COVID-19 remains globally pandemic, and although several meta-analyses have explored the association between vitamin D and COVID-19 relative to clinical outcomes, a unified view has not yet emerged. To summarize the evidence for associations between vitamin D levels and COVID-19-related clinical outcomes and to assess the strength and validity of these associations. PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews databases were searched from January 1, 2020, to June 15, 2024. Two reviewers independently extracted data and assessed study quality. Low vitamin D levels increased the risk of infection by 1.26- to 2.18-fold, the risk of severe illness by 1.50- to 5.57-fold, the risk of intensive care unit (ICU) admission by more than 2-fold, and the risk of death by 1.22- to 4.15-fold. In addition, patients with vitamin D deficiency had an average increase in length of hospital stay of 0.54 days compared with patients with high vitamin D levels. Overall, vitamin D supplementation may reduce severity (eg, ICU admissions, need for mechanical ventilation) and shorter length of hospital stay but has a nonsignificant effect on infection and mortality rates. In addition, there were significant differences in vitamin D levels between individuals testing positive for COVID-19 and those testing negative (mean difference [MD] = -3.22 ng mL-1; 95% CI, -5.18 to -1.25), those with severe cases and those with mild cases (MD = -4.60 ng mL-1; 95% CI, -5.49 to -3.71), and nonsurvivors and survivors of COVID-19 infection (MD = -6.59 ng mL-1; 95% CI: -8.94 to -4.24). Low vitamin D levels are associated with higher infection rates, more severe disease, and higher mortality rates among individuals with COVID-19, whereas vitamin D supplementation may reduce patients' disease severity. The beneficial effects on infection rates and mortality remain to be further explored, however, in higher-quality, randomized controlled studies. Nonetheless, caution is warranted because the methodological quality of most meta-analyses and the level of evidence for most outcomes are very low. PROSPERO registration No. CRD42022385036.