Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis
Christiano Argano, Raffaella Mallaci Bocchio, Giuseppe Natoli, Salvatore Scibetta, Marika Lo Monaco, Salvatore Corrao
Pharmaceuticals, doi:10.3390/ph16010130
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-19related 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.
Funding: The ENFARMA S.R.L. company contributed only to publication costs and did not influence in any way the conception and writing of the manuscript.
Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
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'abstract': '<jats:p>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.</jats:p>',
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