Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-Analysis

This meta-analysis found vitamin D deficiency/insufficiency increased susceptibility to COVID-19 and severe COVID-19, however there was a high risk of bias and heterogeneity. 

• 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis. 
• Vitamin D deficiency/insufficiency increased the odds of developing COVID-19, severe disease and death.  
• 25-hydroxy vitamin D (25(OH)D) concentrations were lower in individuals with COVID-19 compared to controls, in patients with severe COVID-19 compared to controls with non-severe COVID-19, and in non-survivors compared to survivors.  
• The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses.  
• Discrepancies in timing of vitamin D testing, definitions of severe COVID-19 and vitamin D deficiency/insufficiency partly explained the heterogeneity.  

76 observational studies including almost 2 million adults.

The authors point out that risk of bias was very high in all studies and that the main source was the timing of vitamin D testing in relation to onset of COVID-19 which makes it difficult to determine if the vitamin D levels were a result of the illness itself.

Multiple observational studies involving nearly two million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.

• A systematic review and meta-analysis was conducted to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment. 
• CINHAL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science were searched up to 30.05.2021 for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. 

Dissanayake HA, de Silva NL, Sumanatilleke M, de Silva SDN, Gamage KKK, Dematapitiya C, Kuruppu DC, Ranasinghe P, Pathmanathan S, Katulanda P. Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1484-1502. doi: 10.1210/clinem/dgab892. PMID: 34894254; PMCID: PMC8689831.