Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis

Systematic review and meta-analysis of studies in individuals tested for SARS-CoV-2 or diagnosed with COVID-19, including hospitalized and non-hospitalized populations from multiple regions such as Asia, the United States, and Europe. The evidence base included studies assessing baseline serum 25(OH)D status and studies reporting vitamin D supplementation exposure.

Vitamin D supplementation was evaluated in heterogeneous regimens across included studies, including calcifediol and vitamin D3 (cholecalciferol). Dose, frequency, route, and duration were not consistently reported in the source packet.

Vitamin D supplementation was associated with lower COVID-19 severity and mortality, while low baseline vitamin D status was associated with higher infection, severity, and mortality risk. For severity, the pooled association was SRR 0.38 (95% CI 0.20-0.72; 6 studies), and for mortality it was SRR 0.35 (95% CI 0.17-0.70; 8 studies), both indicating reduced risk with supplementation. Low baseline vitamin D was associated with higher infection risk, SRR 2.18 (95% CI 1.55-3.06). The authors concluded that these findings are suggestive but not causal, and that randomized controlled trials are needed to confirm benefit.

The evidence was heterogeneous and relied heavily on observational data, limiting causal inference. Supplement regimens were variable and dose-response relationships were not clear. The review also notes the need for dedicated randomized controlled trials and more standardized reporting.