Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 34160843 · doi:10.1111/cen.14540
What was done
Databases were searched from 1 January 2019 to 3 December 2020 for observational studies assessing the link between vitamin D deficiency and COVID-19 infection severity. Independent reviewers extracted data across 17 observational studies comprising 2,756 patients. Outcomes examined were mortality, hospital admission, intensive care unit admission, and length of hospital stay.
What was found
Compared to non-deficient status, vitamin D deficiency was associated with: - Increased mortality: OR 2.47 (95% CI: 1.50–4.05; 12 studies) and HR 4.11 (95% CI: 2.40–7.04; 3 studies). - Higher rates of hospital admission: OR 2.18 (95% CI: 1.48–3.21; 3 studies). - Longer hospital stays: difference of 0.52 days (95% CI: 0.25–0.80; 2 studies). Subgroup analyses by deficiency cut-offs, latitude, and geographic location showed consistent trends.
Why it matters
This review pools early pandemic observational data showing a consistent association between low vitamin D levels and severe COVID-19 outcomes, highlighting the need for interventional trials to evaluate whether supplementation improves clinical outcomes.
Limits
All included data derive from observational studies, precluding causal inference due to confounding factors like age, obesity, socioeconomic status, and reverse causation (acute phase drop in 25-hydroxyvitamin D). Studies varied in definitions and thresholds for deficiency, and interventional supplementation was not assessed.
Cited by
- supports Observational studies show that COVID-19 patients with vitamin D deficiency had higher rates of hospitalization, mechanical ventilation, and mortality.