Association Between Vitamin D Supplementation or Level and Susceptibility to COVID-19 Infection Including Clinical Course, Morbidity and Mortality Outcomes: Systematic Review
Leads: Dr Amy Grove, Prof Aileen Clarke (Public Health)
Rapid response research.
Dates: April 2020 - November 2020
Interest is mounting regarding the association of vitamin D supplementation or level with susceptibility to COVID-19 infection due to the recognised modulating effects of vitamin D on the immune system and immune response. Given the uncertainty, it was timely to systematically review and critically appraise all peer-reviewed published evidence to assess the association of vitamin D supplementation or level with susceptibility to COVID-19 infection including clinical course, morbidity and mortality outcomes.
Policy and Practice Partners:
The review was informed and scoped following discussions with members from three policy and practice groups; the Welsh Ambulance Services NHS Trust, Health Improvement Directorate Public Health England and Medicines Evidence and Advice at NICE. The review was funded and conducted independently of these groups.
Public Health England.
Aims and Objectives:
The study aimed to: systemically review and critically appraise published studies of the association between vitamin D supplementation or level and susceptibility to COVID-19 infection, including clinical course, morbidity and mortality outcomes.
We undertook a systematic review to answer the following question: is vitamin D supplementation or level associated with susceptibility to severe beta-coronavirus infection (Severe Acute Respiratory Syndrome [SARS-CoV], Middle East Respiratory Syndrome [MERSCoV], Severe Acute Respiratory Syndrome two [SARS-CoV-2]) including clinical course, morbidity and mortality outcomes? We searched 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. Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Downs and Black Quality Assessment Checklist. Identified studies were too heterogeneous to facilitate pooling of study data.
Searches elicited 449 papers, 59 studies were eligible full text assessment and four 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=1,486) showing cases with confirmed/probable COVID-19 reported lower vitamin D supplementation. All studies were at high/unclear risk of bias.
We found no robust evidence of a negative association between vitamin D and COVID-19 infection. No relevant randomised control 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 infection are as yet unproven despite increasing interest from the media and academic community.
Implications for Implementation:
Following publication of the review, we anticipate that the findings will inform the update of the COVID-19 rapid guideline: vitamin D NICE guideline [NG187]. Available at: https://www.nice.org.uk/guidance/ng187
Grove A, Osokogu O, Al-Khudairy L, Mehrabian A, Zanganeh M, Brown A, Court R, Taylor-Phillips S, Uthman O, McCarthy N, Kumar S, Clarke A. Association between vitamin D supplementation or level and susceptibility to COVID-19 infection including clinical course, morbidity and mortality outcomes? A systematic review. BMJ Open [Under Editorial Review].