Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies

Vitamin D deficiency and obesity increases risk of testing positive for COVID-19.

• The systematic search led to 43 eligible studies from 737 retrieved, retrospective or observational studies (n = 612,601 patients), analyzing the effect of vitamin D deficiency or insufficiency and COVID-19 disease (infection, severity, or mortality). Among them, 8 reported on the therapeutic effect of supplementation on severity and mortality rate.
• Among subjects with deficient vitamin D values, risk of COVID-19 infection was higher compared to those with replete values.
• The funnel plot shows a minimal risk of publication bias for the primary endpoint analysis.
• Where deficient (<20 ng/mL) vitamin D cutoff was used, the risk of infection was 50% higher compared to subjects with nondeficient values.
• Vitamin D deficiency was also associated with worse severity and higher mortality than in nondeficient patients.

43 eligible studies including 612,601 subjects

• It is important to consider that the studies included are limited to the inclusion exclusion criteria of the study design and therefore may miss important studies with slightly different design but meaningful data.
• In addition, in order to conduct a meta-analysis the studies included must have similar endpoints to extract and in doing so researchers may group together studies that are not the same but will be analyzed as the same which can lead to skewed conclusions.
• A meta-analysis only includes studies that have been published and therefore information gathered may be subject to publication bias. This means that studies that show no effect or the opposite of the expected effect may not be published and therefore not included.

Reduced vitamin D values resulted in a higher infection risk, mortality and severity of COVID-19 infection. Supplementation may be considered as preventive and therapeutic measure.

• This study was performed by applying the Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE) guidelines. It also complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P).
• PubMed, the Cochrane Library, and EMBASE were searched from inception until January 31, 2021, for observational or clinical studies reporting the prognosis (and therapeutic effect) of COVID-19 infection in patients with deficient vitamin D levels.
• The search terms were as follows: ((vitamin D [MeSH Terms]) or (vitamin D) or (25OH vitamin D) OR cholecalciferol OR ergocalciferol OR calcitriol)) and (“covid-19”).
• The infection rate, severity and death from COVID-19 infection were pooled to provide an odds ratio with a 95 % confidence interval (OR 95 % CI). An OR > 1 was associated with the worst outcome in deficient compared with nondeficient patients.
• The study’s primary outcome was COVID-19 infection risk in vitamin D-deficient vs nondeficient patients. Secondary endpoints were severity (intensive care unit and/or mechanical ventilation), death, and therapeutic effect of vitamin D supplementation in COVID-19-affected patients.

Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol. 2021 Jul;211:105883. doi: 10.1016/j.jsbmb.2021.105883. Epub 2021 Mar 26. PMID: 33775818; PMCID: PMC7997262.