Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis

This combined meta-analysis and trial sequential analysis found that vitamin D supplementation significantly reduced the risk of ICU admission in patients hospitalized with COVID-19. 

• 5 RCTs met the eligibility criteria and were included in the analyses. Three out of five studies included a small number of patients; however, one study included more than 800 patients, and another included 240 subjects. 
• Vitamin D intervention ranged from 5000 to 200 000 IU/day, and duration of supplementation ranged from 8 to 30 days. 
• Results of meta-analysis revealed a strong association between vitamin D supplementation and protective effect on admission to the ICU, as well as on reduced risk of death. 
• Further analysis by TSA confirmed the effect of vitamin D on reducing the risk of ICU admission but showed a false-positive association between vitamin D supplementation and mortality, indicating these results could not be confirmed and require further studies.  

5 randomized controlled clinical trials, including a total of 1400 patients hospitalized with COVID-19 infection. Three of the studies were conducted in Spain, one in Brazil, and one in Saudi Arabia.

• A small number of studies were included, and only one study had a low risk of bias, and statistical heterogeneity and a large effect size were observed.  
• A wide range of vitamin D doses were used in the studies, including up to 200,000 IU/day. 
• The authors noted that the effect of vitamin D on COVID-19 mortality needs to be further examined in studies with consistent sample size and longer duration of vitamin D supplementation, and the time until follow-up evaluations should be sufficient to achieve adequate vitamin D serum levels. 

In conclusion, the positive results highlighted again and now validated by TSAs suggest that an indisputable association between vitamin D supplementation and the protective effect on ICU admission can be considered definitive evidence. On the contrary, further studies are needed to assess the utilization of vitamin D regarding the risk of death in patients hospitalized with COVID-19.

• A meta-analysis and trial sequential analysis (TSA) was conducted to examine the association between vitamin D supplementation and risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19 infection.  
• PubMed, CT.gov, Embase, and ICTRP were searched on September 20, 2022, for randomized clinical trials (RCTs) involving patients 18 years or older that were hospitalized with COVID-19 and investigated vitamin D supplementation in comparison with placebo, standard of care, or no treatment. 

Argano C, Mallaci Bocchio R, Natoli G, Scibetta S, Lo Monaco M, Corrao S. Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis. Pharmaceuticals, 2023, Jan 16;16(1):130. doi: 10.3390/ph16010130.