Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 35004568 · doi:10.3389/fpubh.2021.736665
What was done
A systematic review and meta-analysis of observational studies was performed searching PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprint repositories up to March 31, 2021. Studies evaluating associations between serum 25-hydroxyvitamin D levels (insufficiency <75 nmol/L, deficiency <50 nmol/L, or severe deficiency <25 nmol/L) and primary endpoints (ICU admission, mortality) or secondary endpoints (SARS-CoV-2 infection, COVID-19 hospitalization) were analyzed.
What was found
Fifty-four studies (49 peer-reviewed, 5 preprints) with 1,403,715 total individuals were included. Associations were reported as follows: - ICU admission: severe deficiency OR 2.63 (95% CI 1.45–4.77), deficiency OR 2.16 (95% CI 1.43–3.26), insufficiency OR 2.83 (95% CI 1.74–4.61) across 27 studies. - Mortality: severe deficiency OR 2.60 (95% CI 1.93–3.49), deficiency OR 1.84 (95% CI 1.26–2.69), insufficiency OR 4.15 (95% CI 1.76–9.77) across 35 studies. - SARS-CoV-2 infection: severe deficiency OR 1.68 (95% CI 1.32–2.13), deficiency OR 1.83 (95% CI 1.43–2.33), insufficiency OR 1.49 (95% CI 1.16–1.91) across 17 studies. - COVID-19 hospitalization: severe deficiency OR 2.51 (95% CI 1.63–3.85), deficiency OR 2.38 (95% CI 1.56–3.63), insufficiency OR 1.82 (95% CI 1.43–2.33) across 9 studies. Primary endpoint results remained consistent in subgroups of Caucasian patients, high-quality studies, and studies with adjusted estimates.
Why it matters
This meta-analysis aggregates data from over 1.4 million individuals to document a consistent observational association between low vitamin D levels and increased risk of SARS-CoV-2 infection and severe COVID-19 outcomes.
Limits
All included data derive from observational studies, precluding causal conclusions. Vitamin D is an acute-phase reactant subject to reverse causation during acute infection, and residual confounding from comorbidities, adiposity, and socioeconomic factors cannot be excluded. Five included records were unreviewed preprints.
Cited by
- supports Observational studies show that COVID-19 patients with vitamin D deficiency had higher rates of hospitalization, mechanical ventilation, and mortality.