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

PLoS ONE
Q1
Jul 2022
Citations:60
Influential Citations:1
Systematic Reviews / Meta-Analyses
85
S2 IconPDF Icon

Enhanced Details

Methods
38 independent studies included up to April 2021; study designs included 2 randomized controlled trials and 27 cohort studies; total participants across analyses: 207587; participants included individuals tested for SARS-CoV-2 or COVID-19 positive; data included baseline 25(OH)D status or VD supplementation; most studies were retrospective; studies conducted across Asia, the USA and Europe.
Results
Vitamin D supplementation was significantly associated with lower risk of severe Covid-19 disease (SRR 0.38, 95% CI 0.20-0.72; 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70; 8 studies). No clear dose–response differences: regular dosing remained significant; higher doses did not show additional benefit. Greater mortality risk reduction with supplementation observed in older adults and at higher latitudes. Baseline 25(OH)D deficiency was associated with higher risk of SARS-CoV-2 infection (SRR 2.18; 95% CI 1.55-3.06) and with more severe disease and mortality. Results tended to be stronger in prospective/adjusted studies. Dedicated randomized trials are needed to confirm causality. Seasonal analyses suggested stronger effects in winter; benefits may be smaller in summer. Practically, assessing vitamin D status and considering targeted supplementation may benefit at‑risk populations, especially in winter, while acknowledging reliance on observational data and study heterogeneity.
Limitations
Significant heterogeneity across studies; majority of data are observational with potential bias; possible selection bias from 25(OH)D measurement; some analyses showed publication bias; variability in supplementation regimens and dosing; limited randomized trial data; potential reverse causation; generalizability largely to hospitalized/tested populations; data limited to studies through April 2021.

Abstract

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for ...