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

DOI record: { "DOI": "10.3390/ph16010130", "ISSN": [ "1424-8247" ], "URL": "http://dx.doi.org/10.3390/ph16010130", "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>", "alternative-id": [ "ph16010130" ], "author": [ { "ORCID": "http://orcid.org/0000-0003-2662-8931", "affiliation": [], "authenticated-orcid": false, "family": "Argano", "given": "Christiano", "sequence": "first" }, { "affiliation": [], "family": "Mallaci Bocchio", "given": "Raffaella", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-7723-5380", "affiliation": [], "authenticated-orcid": false, "family": "Natoli", "given": "Giuseppe", "sequence": "additional" }, { "affiliation": [], "family": "Scibetta", "given": "Salvatore", "sequence": "additional" }, { "affiliation": [], "family": "Lo Monaco", "given": "Marika", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5621-1374", "affiliation": [], "authenticated-orcid": false, "family": "Corrao", "given": "Salvatore", "sequence": "additional" } ], "container-title": "Pharmaceuticals", "container-title-short": "Pharmaceuticals", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 1, 16 ] ], "date-time": "2023-01-16T07:29:55Z", "timestamp": 1673854195000 }, "deposited": { "date-parts": [ [ 2023, 1, 16 ] ], "date-time": "2023-01-16T08:36:12Z", "timestamp": 1673858172000 }, "funder": [ { "name": "ENFARMA S.R.L. company" } ], "indexed": { "date-parts": [ [ 2023, 1, 17 ] ], "date-time": "2023-01-17T06:12:48Z", "timestamp": 1673935968912 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2023, 1, 16 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2023, 1 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 1, 16 ] ], "date-time": "2023-01-16T00:00:00Z", "timestamp": 1673827200000 } } ], "link": [ { "URL": "https://www.mdpi.com/1424-8247/16/1/130/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "130", "prefix": "10.3390", "published": { "date-parts": [ [ 2023, 1, 16 ] ] }, "published-online": { "date-parts": [ [ 2023, 1, 16 ] ] }, "publisher": "MDPI AG", "reference": [ { "key": "ref_1", "unstructured": "(2022, September 22). 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