Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

This meta-analysis suggests that low serum 25-OHD level was associated with higher rate of COVID-19 infection, disease severity, and mortality.

To assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with COVID-19 susceptibility COVID-19, severity, and mortality.

• Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group.
• Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD.
• Low serum 25-OHD was associated with higher mortality.
• Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender and diabetes.

There were 14 studies including 999,179 participants.

• 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 This means that studies that show no effect or the opposite of the expected effect may not be published and therefore not included.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 retrospective design of the studies presents as a potential source of bias.
• The cut-off point slightly varies among the pooled analysis.
• Potential unaccounted confounders may cause bias in the studies, for example, bedridden patients often have low serum 25-OHD compared to the healthy counterpart.
• Large and small studies were weighted equally.

The meta-regression analysis was also based on a relatively small number of studies

In conclusion, low serum 25-OHD level was associated with higher rate of COVID-19 infection, severe presentation, and mortality.

• The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used in developing and conducting this systematic review.
• The inclusion criteria were: (1) published observational retrospective and prospective studies, (2) information on serum 25-OHD with a clear cut-off value ranging from 20 to 30 ng/mL, (3) comparing patients with COVID-19 vs non-COVID-19 OR severity in COVID-19 patients OR mortality in COVID-19 patients.
• A systematic search of the literature search was done using PubMed, Scopus, and Embase databases were performed with keywords “COVID-19” OR “SARS-CoV-2” OR “2019-nCoV” AND “Vitamin D” on 9 December 2020.
• Data extracted included first author, publication year, design, age, male (gender), hypertension, diabetes, serum 25-OHD status, the outcome of interest and its effect estimates.
• Low serum 25-OHD refers to participants with serum 25-OHD below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity.
• The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19. Susceptibility was calculated by comparing the COVID-19 positive cohort with the COVID-19 negative cohort. Severe COVID-19 was defined according to the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation.
• Risk of bias assessment was performed by two independent authors using the Newcastle-Ottawa Scale (NOS).

Akbar MR, Wibowo A, Pranata R, Setiabudiawan B. Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis. Front Nutr. 2021 Mar 29;8:660420. doi: 10.3389/fnut.2021.660420. PMID: 33855042; PMCID: PMC8039288.