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

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.