Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis
Argano et al.,
Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and..,
Pharmaceuticals, doi:10.3390/ph16010130
Meta analysis and trial sequential analysis of 5 vitamin D RCTs, showing significantly lower mortality and ICU admission with treatment. Only a small subset of the 25 RCTs are included. Note that
[Nogués] uses randomization by ward, was censored by the Lancet, and was later reworded as an observational trial. The groups are relatively well matched, with only baseline vitamin D levels (median 13 vs. 12) showing a significant difference (matching is better than many trials that use the term randomized for their randomization without censorship). For more details see
[Nogués].
Currently there are
104 vitamin D studies and meta analysis shows:
risk of death, 51.0% lower, OR 0.49, p < 0.001, RR approximated with OR.
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risk of ICU admission, 72.0% lower, OR 0.28, p < 0.001, RR approximated with OR.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Argano et al., 16 Jan 2023, peer-reviewed, 6 authors.
Contact:
chargano@yahoo.it (corresponding author).
Abstract: pharmaceuticals
Systematic Review
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 1, * , Raffaella Mallaci Bocchio 1 , Giuseppe Natoli 1 , Salvatore Scibetta 1 ,
Marika Lo Monaco 1,2 and Salvatore Corrao 1,2
1
2
*
Citation: 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, 16,
130. https://doi.org/10.3390/
ph16010130
Academic Editor: Julia O. Fedotova
Internal Medicine Department iGR, National Relevance Hospital Trust, ARNAS Civico,
Di Cristina e Benfratelli, 90127 Palermo, Italy
Dipartimento di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza
“G. D’Alessandro”, PROMISE, University of Palermo, 90127 Palermo, Italy
Correspondence: chargano@yahoo.it; Tel.: +39-091-655-2065; Fax: +39-091-666-3167
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-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.
Keywords: vitamin D; COVID-19; ICU hospitalization; mortality; meta-analysis; trial sequential analysis
Received: 23 November 2022
Revised: 27 December 2022
Accepted: 31 December 2022
Published: 16 January 2023
Copyright: © 2023 by the authors.
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Attribution (CC BY) license (https://
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