Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis
What this study found
Vitamin D supplementation during hospitalization for COVID-19 reduced ICU admission risk (pooled effect 0.28, 95% CI 0.20-0.39) with substantial heterogeneity (I2 = 74.2%). Trial sequential analysis shows the ICU result is conclusive. Mortality risk also reduced (0.49, 95% CI 0.34-0.72), but TSA indicated further studies are needed to confirm mortality benefit. Conclusion: There is a definitive association between vitamin D supplementation and reduced ICU admission in hospitalized COVID-19 patients; mortality benefit remains uncertain and requires more evidence.
- Study & population
- Five randomized controlled trials in adults hospitalized with COVID-19; study designs were randomized trials (some multicenter, some single-center) with varying allocation ratios.
- Intervention
- Sabico 2021: vitamin D3 5,000 IU/day vs 1,000 IU/day for 14 days.
- Key limitation
- Small number of trials (n=5) with varied regimens and populations; heterogeneity in vitamin D formulations (D3 vs calcifediol) and dosing; some trials were single-center; risk-of-bias concerns across several trials; mortality result not yet definitively proven by TSA; findings limited to hospitalized adults.
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Open PDFOriginal abstract
Background: The COVID-19 pandemic represents one of the world’s most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. Methods: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. Results: We identified 78 bibliographic citations. After the reviewers’ screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34–0.72) and 0.28 (0.20–0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. Discussion: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.