Vitamin D supplementation for managing COVID-19 in patients with vitamin D deficiency: a systematic review and meta-analysis of randomised controlled trials.

objectivesVitamin D deficiency is prevalent among the population. Previous studies have shown that vitamin D supplementation might be useful for treating COVID-19 infection. Therefore, we performed a meta-analysis to explore vitamin D supplementation efficacy in treating COVID-19 patients with vitamin D deficiency.

designSystematic review and meta-analysis DATA SOURCES: PubMed, Cochrane Library, Embase and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials exploring vitamin D supplementation for patients with COVID-19 and vitamin D deficiency. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers employed standardised methods to search, screen and code the included studies. The primary outcomes included mortality during follow-up, 28-day mortality, need for mechanical ventilation and intensive care unit (ICU). The secondary outcome included length of stay in hospital and ICU. The risk of bias was assessed using the Risk of Bias 2 tool. Depending on the level of heterogeneity, either a random-effects model or a fixed-effects model was applied. The findings were summarised using Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profiles and synthesised qualitatively.

resultsA total of nine studies, comprising 870 participants, were included in the analysis. The pooled results indicated that vitamin D supplementation was associated with a lower risk of mortality (risk ratio 0.76; 95% CI 0.60 to 0.97). However, this apparent benefit was not robust when examined through the leave-one-out method and trial sequential analysis. Regarding other outcomes, there was no statistically significant difference between vitamin D supplementation and no supplementation in terms of 28-day mortality, the need for mechanical ventilation and ICU admission. Vitamin D supplementation was associated with a 0.41 day shorter length of stay in the ICU (mean difference -0.41; 95% CI -1.09 to 0.28) and a 0.07 day shorter length of stay in the hospital (mean difference -0.07; 95% CI -0.61 to 0.46) compared with no supplementation; however, neither difference was statistically significant.

conclusionBased on evidence of low to moderate quality, vitamin D supplementation reduced the mortality rate during follow-up in COVID-19 patients with vitamin D deficiency. However, it did not improve 28-day mortality, nor did it reduce the need for mechanical ventilation and ICU admission, or the length of stay in the ICU and hospital. PROSPERO REGISTRATION NUMBER: CRD42024573791.