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Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis

Take Home Message

In this meta-analysis it is suggested that Vitamin D deficiency is associated with greater severity of COVID‐19 infection.


To evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID-19) infection.



  • The overall risk of bias of the included studies was high due to a lack of control of confounding variables
  • Vitamin D deficiency was associated with significantly higher mortality, higher rates of hospital admission and longer hospital stays and no significant difference in ICU admissions.
  • The significant difference between patients with vitamin D deficiency and nondeficiency levels remained in most of the subgroup analyses (25(OH)D cut‐offs for the definition of vitamin D deficiency, geographic location and latitude).



Seventeen observational studies with 2756 eligible adult patients who met the inclusion criteria were included in the analyses.

Things to Keep in Mind

  • 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 This means that studies that show no effect or the opposite of the expected effect may not be published and therefore not included
  • These studies were observational in nature and were not conducted under an experimental design therefore there was no control for confounding variables such as age, other illness, obesity, etc.


Author’s Conclusions

Vitamin D deficiency is associated with greater COVID‐19 infection severity as measured by rates of mortality, hospital admission and duration of hospital stay. Longitudinal interventional studies are warranted to determine if vitamin D supplementation can decrease COVID‐19 infection severity.

Study Design

  • The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines were followed to report this systematic review and meta‐analysis.
  • A comprehensive database search, including MEDLINE(R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations and Daily, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus, from 1 January 2019 to 3 December 2020 was conducted. Reference mining of existing systematic reviews/meta‐analyses, preprint medical literature from medRxiv. org, and relevant primary studies were conducted to identify additional studies.
  • Eligible studies (1) included patients with laboratory‐confirmed COVID‐19 diagnosis (polymerase chain reaction [PCR]); (2) documented evaluation of total serum 25‐hydroxyvitamin D (25(OH)D) level within 3 months of COVID‐19 diagnosis; (3) availability of a comparison group: comparing vitamin D deficiency to nondeficiency (includes normal vitamin D status and insufficiency); and (4) reported outcomes of interest (mortality, hospital admission, length of hospital stay and intensive care unit [ICU] admission).
  • The 25(OH)D cut‐offs for defining vitamin D deficiency were defined by each study.
  • The risk of bias of the included studies using the modified Newcastle–Ottawa Scale, in terms of representativeness of study cohort, ascertainment of exposure, comparability between groups, outcome data source and assessment of outcome



Wang Z, Joshi A, Leopold K, Jackson S, Christensen S, Nayfeh T, Mohammed K, Creo A, Tebben P, Kumar S. Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis. Clin Endocrinol (Oxf). 2021 Jun 23:10.1111/cen.14540. doi: 10.1111/cen.14540. Epub ahead of print. PMID: 34160843; PMCID: PMC8444883.

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Research Summaries

Association Between Vitamin D Supplementation and COVID-19 Infection and Mortality

Association Between Vitamin D Supplementation and COVID-19 Infection and Mortality Take Home Message Among VA (Veterans Administration) patients, vitamin D3 and vitamin D2 supplementation reduced the associated risk of COVID-19 infection