Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis

Abstract

To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case-control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I² 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I² 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.

Keywords: 1,25-dihydroxyvitamin D; 25-hydroxyvitamin D; SARS-CoV-2; meta-analysis; systematic review.

Figure 1. Flowchart of study selection.

Figure 2. Association between serum vitamin D levels and mortality in patients with COVID-19 according to 25(OH)D cutoff level.

Figure 3. Association between serum vitamin D levels and mortality in patients with COVID-19, including studies that adjusted the analysis for age and at least one more confounder (obesity, hypertension, diabetes, renal disease, and cardiovascular disease) and studies without adjustment for confounders. (A) Analysis performed by 25(OH)D cutoff level, including only studies with adjustments; (B) analysis performed by 25(OH)D cutoff level, including studies without adjustments.

Figure 4. Funnel plot using data from 21 studies associating serum vitamin D levels and mortality. Four studies were included twice, as they analyzed two 25(OH)D cutoff levels.