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

Abstract

Background: The COVID-19 pandemic represents one of the world’s most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. Methods: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. Results: We identified 78 bibliographic citations. After the reviewers’ screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34–0.72) and 0.28 (0.20–0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. Discussion: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.

Evaluation of 25-hydroxyvitamin D (25(OH)D) levels before and during the COVID-19 pandemic: A cross-sectional study and trend analysis involving 86,772 samples

“…As such, vitamin D is a vital component in the human body that acts as both a vitamin and a steroid hormone. Thus, policies must be created to raise awareness of the community about 25(OH)D in cases of partial or complete closure [50][51][52]. There is a need for multicenter studies with larger populations covering different regions to strengthen and support our results.…”

Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

“…Numerous evidences con rm vitamin D insu ciency is associated with greater severity of COVID-19 infection, even the more recent Omicron subvariant of COVID-19(46, 47, 48). Vitamin D administration has been found to be associated with less severe COVID-19 and resulted in a decreased risk of death and admission to intensive care units in patients with COVID-19 (49). In addition, fatty acid metabolism is a crucial event for many viruses to complete their life cycle, and a common consequence of infection by many viruses is to change the nature of lipid metabolism usually from fatty acid oxidation to fatty acid synthesis (50).…”

The Role of Diet and Specific Nutrients during the COVID-19 Pandemic: What Have We Learned over the Last Three Years?

“…In contrast to preventive lower dose supplementation, clinical intervention trials with higher doses of vitamin D in hospitalized COVID-19 patients revealed some positive meta-analytical evidence especially on the risk for ICU admission [ 83 , 85 , 91 , 92 , 93 ] although not all meta-analyses showed significant beneficial effects [ 87 , 89 ] ( Table 1 ). In addition, it is suggested that COVID-19 patients may rather benefit from receiving a daily or maintained in time vitamin D dose in contrast to a single vitamin D dose, which does not seem to have any effect on the health status of the patients studied [ 121 , 122 ].…”