Is the Vitamin D Status of Patients with COVID-19 Associated with Reduced Mortality? A Systematic Review and Meta-Analysis

his meta-analysis found that overall vitamin D deficiency was associated with reduced COVID-19 mortality. However, when confounding factors such as age, sex, and pre-existing conditions were taken into account, there was no significant association between vitamin D status and death in COVID-19 patients.

• 21 studies were included in the analysis, two of which were case-control studies and 19 of which were cohort studies.  
• Overall, Vitamin D deficiency was associated with COVID-19 mortality, but not when the analysis was adjusted to vitamin D cutoff levels of < 10 or < 12 ng/mL (severely deficient).  
• No association between vitamin D status and mortality was seen when only studies that adjusted for the effect of confounders were analyzed; however, when the analysis included studies without adjustments for confounding factors, an association between vitamin D level and increased risk of death in COVID-19 patients was observed. 

21 studies (19 cohort and 2 case-control) including 6,096 adult patients hospitalized with COVID-19 who had serum vitamin D levels measured close to the date of diagnosis. 

All studies included were observational, and there was considerable variation between studies and methodology, including different outcome measures and serum vitamin D cutoff levels. 

In conclusion, the results of the present study showed that, overall, vitamin D status was associated with mortality in patients with COVID-19, but not when the analysis included studies that adjusted measures of effect for confounding factors. Confounders may have led to the conclusion of the detrimental effects of low serum 25(OH)D levels in patients with COVID-19 observed in some previous studies. Large randomized clinical trials are needed to assess the effects of vitamin D levels (including those of 1,25[OH]2 D) on mortality in patients hospitalized with COVID-19.

• This systematic review and meta-analysis was carried out to assess the association between serum vitamin D status and mortality in patients with COVID-19.  
• PubMed and Embase were searched for studies examining the effect 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. 
• Studies meeting the following criteria were included: included hospitalized patients >18 years of age with confirmed COVID-19 diagnosis, and with vitamin D status identified as “deficient” or “insufficient” by measurement of serum vitamin D (25[OH]D) levels close to the date of the COVID-19 diagnosis (specifically, up to 30 days before or up to 7 days after the diagnosis); enrolled patients with COVID-19 and vitamin D status identified as “sufficient,” who were used for comparison; examined the association between vitamin D status and mortality. 

Bignardi PR, de Andrade Castello P, de Matos Aquino B, Delfino VDA. Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis. Arch Endocrinol Metab. 2023 Mar 10;67(2):276-288. doi: 10.20945/2359-3997000000588.