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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

Background:

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.

Co-Funding Partners:

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.

Methods:

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.

Main Results:

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.

Conclusions:

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

Protocol Registration:

PROSPERO CRD42020182876.

Publication:

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].

Tue 08 Dec 2020, 16:19 | Tags: Aileen Clarke Public Health Amy Grove