Effect of vitamin D supplementation on clinical outcomes in adult patients with COVID-19: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

The COVID-19 pandemic has emerged as a major global health crisis. Vitamin D, a crucial fat-soluble vitamin, has been recommended for COVID-19 patients, though evidence of its effectiveness is inconsistent. This systematic literature review and meta-analysis aimed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes. A comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Primary outcomes included mortality and hospital length of stay, while secondary outcomes encompassed C-reactive protein (CRP), ferritin, D-dimer, hemoglobin (Hb) concentrations, and lymphocyte, neutrophil, and platelet counts. Data analysis was performed using Stata™ Version 14. A total of 16 trials were analyzed. The meta-analysis revealed that vitamin D supplementation significantly reduced hospital length of stay (mean difference = -1.16; 95% confidence interval [CI]: -2.23, -0.09; p = .033) with significant heterogeneity (I² = 69.2%, p = .002). Subgroup analysis showed a more pronounced reduction in studies with vitamin D dosages ≤10 000 international units (IU) (mean difference = -1.27; 95% CI: -1.96, -0.57; p < .001) and in patients over 60 years old (mean difference = -1.84; 95% CI: -2.53, -1.14; p < .001). Additionally, vitamin D significantly reduced CRP concentrations in older adults (>60 years) (mean difference = -1.13; 95% CI: -2.07, -0.18; p = .019). No significant changes were found in ferritin, D-dimer, Hb concentrations, or in lymphocyte, neutrophil, and platelet counts (p > .05). In conclusion, while vitamin D supplementation did not significantly affect most COVID-19-related biomarkers, however, it reduces the length of hospital stay.