Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis

Pharmaceuticals
Q1
Jan 2023
Citations:44
Influential Citations:1
Systematic Reviews / Meta-Analyses
84
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Enhanced Details

Methods
Five randomized controlled trials in adults hospitalized with COVID-19; study designs were randomized trials (some multicenter, some single-center) with varying allocation ratios. Participants were adults (roughly 20–80+ years), mixed sexes.
Intervention
Sabico 2021: vitamin D3 5,000 IU/day vs 1,000 IU/day for 14 days. Castillo 2020: calcifediol-based regimen (calcifediol dosing equivalent to about 21,280 IU/day on days 1, 3, and 7, then weekly until discharge or ICU admission). Torres 2022: vitamin D3 10,000 IU/day vs 2,000 IU/day for 8–29 days. Murai 2021: a single oral dose of vitamin D3 200,000 IU versus placebo. Nogues 2021: calcifediol 21,620 IU on day 1 and 10,810 IU on days 3, 7, 15, and 30; placebo. All regimens oral. Durations ranged approximately 2 weeks to 30 days depending on trial.
Results
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.
Limitations
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.

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 cru...