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

Abstract

Context: 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.

Objective: 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.

Data sources: PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews databases were searched from January 1, 2020, to June 15, 2024.

Data extraction: Two reviewers independently extracted data and assessed study quality.

Data analysis: 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).

Conclusions: 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.

Systematic review registration: PROSPERO registration No. CRD42022385036.