The link between COVID-19 and Vitamin D (VIVID): A systematic review and meta-analysis.

This meta-analysis suggested that there is no statistical association between low serum 25(OH)D levels and COVID-19 related health outcomes. However, there was a positive trend between low serum 25(OH)D level and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. Also, average 25(OH)D levels were significantly lower in COVID-19 positive, compared to negative patients.

To assess the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes.

• There was a positive trend between serum 25(OH)D level <20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant.
• Mean 25(OH)D levels was 5.9 ng/ml (95% CI [−9.5, −2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low.
• The trials administer vitamin D doses of 357 to 60,000 IU/day, from one week to 12 months.
• Eight megatrials investigate the efficacy of vitamin D in outpatient populations. Three small trials had inconclusive evidence.

31 observational studies including over 8209 patients, aged 42-81 years

• 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 This means that studies that show no effect or the opposite of the expected effect may not be published and therefore not included.
• The authors identify “scarce evidence” provided from published observational studies, and heterogeneity in the definition of vitamin D deficiency, and the timing of blood withdrawal in relation to the diagnosis of COVID-19.
• The authors identified results from only three randomized controlled trials, and could only meta-analyze results from few observational studies, which downgrades the level of evidence.

While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.

• This was a systematic review and meta-analysis which followed the established Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)Guidelines.
• Before starting the literature review search methods as well as criteria for which studies to include and exclude were established.
• Medline (OVID), Embase.com, CINAHL (EBSCO), and Cochrane until December 18th, 2020, with no limit on language.
• The MESH terms and keywords relevant to vitamin D and COVID-19 were used.
• The primary outcome was mortality rate from COVID-19 infection.
• The secondary outcomes included SARS-CoV-2 positivity, disease severity, need for hospitalization, hospital stay duration, need for ICU admission, ICU stay duration, need for invasive or non-invasive ventilation, time on respirators, time to symptomatic recovery, time to seronegative conversion, and risk of positive seroconversion of family members. In addition, the risk of its complications: acute respiratory distress syndrome, acute respiratory failure, pneumonia, cytokine storm, organ failure, septic shock, disseminated intravascular coagulation, neurological complications, and rhabdomyolysis were evaluated.
• Bias was assessed using the New Castle-Ottawa quality scale to evaluate three main domains: selection, comparability, and outcome/exposure. The quality of the included clinical trials was assessed the Cochrane Risk of bias tool, version 1. The Grading of Recommendations Assessment, Development, and Evaluation working group methodology (GRADE) was used to examine the quality of evidence from included studies for each outcome in the primary analysis.

Bassatne A, Basbous M, Chakhtoura M, El Zein O, Rahme M, El-Hajj Fuleihan G. The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism. 2021 Jun;119:154753. doi: 10.1016/j.metabol.2021.154753. Epub 2021 Mar 24. PMID: 33774074; PMCID: PMC7989070.