Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review
What this study found
Overall, there was no robust evidence that vitamin D supplementation or serum vitamin D level was associated with susceptibility to SARS-CoV-2 infection or with COVID-19 clinical course, morbidity, or mortality. All included studies were observational and at high or unclear risk of bias with limited confounding adjustment. In the UK Biobank analysis, an unadjusted association between vitamin D and COVID-19 disappeared after covariate adjustment, and no study reported an association with severity or mortality. In the Lombardy Parkinson's disease survey, vitamin D intake was reported in 12.4%…
- Study & population
- Systematic review of observational studies from Europe, including data from the UK Biobank, a cross-sectional study in Switzerland, an ecological analysis across multiple European countries, and a case-control survey of Parkinson's disease patients in Lombardy, Italy.
- Intervention
- No randomized vitamin D regimen was tested.
- Key limitation
- The review relied entirely on observational studies, so confounding and bias were major concerns.
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Open PDFOriginal abstract
Objective To systemically review and critically appraise published studies of the association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19, including clinical course, morbidity and mortality outcomes. Design Systematic review. Data sources MEDLINE (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, MedRxiv and BioRxiv preprint databases. COVID-19 databases of the WHO, Cochrane, CEBM Oxford and Bern University up to 10 June 2020. Study selection Studies that assessed vitamin D supplementation and/or low serum vitamin D in patients acutely ill with, or at risk of, severe betacoronavirus infection (SARS-CoV, MERS-CoV, SARS-CoV-2). Data extraction Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Downs and Black Quality Assessment Checklist. Results Searches elicited 449 papers, 59 studies were eligible full-text assessment and 4 met the eligibility criteria of this review. The four studies were narratively synthesised and included (1) a cross-sectional study (n=107) suggesting an inverse association between serum vitamin D and SARS-CoV-2; (2) a retrospective cohort study (348 598 participants, 449 cases) in which univariable analysis showed that vitamin D protects against COVID-19; (3) an ecological country level study demonstrating a negative correlation between vitamin D and COVID-19 case numbers and mortality; and (4) a case–control survey (n=1486) showing cases with confirmed/probable COVID-19 reported lower vitamin D supplementation. All studies were at high/unclear risk of bias. Conclusion There is no robust evidence of a negative association between vitamin D and COVID-19. No relevant randomised controlled trials were identified and there is no robust peer-reviewed published evidence of association between vitamin D levels and severity of symptoms or mortality due to COVID-19. Guideline producers should acknowledge that benefits of vitamin D supplementation in COVID-19 are as yet unproven despite increasing interest.