Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

This meta-analysis suggested that there is a significant relationship between 25(OH)D concentration and SARS-CoV-2 infection, as well as COVID-19 severity and mortality.

To summarize and clarify the evidence on the association between 25(OH)D concentrations and COVID-19 risk and outcomes.

• In studies that were adjusted and nonadjusted for confounders (related factors) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group.
• Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted and nonadjusted for confounders there was a higher severity in the VDD group.
• There was a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed.
• The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent.

• 39 studies were included, with different geographical locations and ethnic backgrounds, including Europe (n = 17 studies), North America (United States) (n = 2), South America (n = 2), West Asia (n = 9), South Asia (n = 4), East Asia (n = 4), and Africa (n = 1).
• Ten studies were of a case-control design, 19 cross-sectional, 2 retrospective cohorts, 2 randomized controlled trials (RCTs), 2 quasi-experimental design, and 4 studies were only descriptive. All studies were conducted in adults, except for 1 study in children and 1 study in pregnant women. A total number of subjects was not indicated

• 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 This means that studies that show no effect or the opposite of the expected effect may not be published and therefore not included.
• This review included studies that were heterogeneous in design, methodology, and statistical approach.
• Most of the studies included were observational, causality cannot be inferred.
• Sex and age are important factors that have been shown to be related to both COVID-19 and 25(OH)D concentrations independently that were not reported in many of the studies.

Although studies were heterogeneous in methodological and statistical approach, and some inherent limitations were present, the findings of the present study indicated a significant relation between 25(OH)D concentration and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. For infection, caution should be taken in interpreting the results due to inherent limitations of studies. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient. Moreover, future studies should investigate the association of COVID-19 with vitamin D in subgroups of age and sex.

• The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used in developing and conducting this systematic review.
• PubMed, Scopus, and Web of Science databases and the first 500 Google Scholar search results were searched up to 26 November 2020, with no restriction in language.
• The following search strategy was used for the search: (Coronavirus or COVID-19 or SARS-CoV-2) AND (vitamin D or 25-OH-D or cholecalciferol or 25-hydroxycholecalciferol or calcitriol or 25-hydroxyvitamin D or hydroxycholecalciferols or 25-hydroxyvitamin D3).
• Quality assessment of observational studies was assessed using the Newcastle–Ottawa Scale

Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CCT, Babajafari S. Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis. Adv Nutr. 2021 Oct 1;12(5):1636-1658. doi: 10.1093/advances/nmab012. Erratum in: Adv Nutr. 2021 Oct 1;12(5):2040-2044. PMID: 33751020; PMCID: PMC7989595.