Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

{ 'indexed': {'date-parts': [[2024, 3, 19]], 'date-time': '2024-03-19T14:33:36Z', 'timestamp': 1710858816475}, 'reference-count': 122, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 11, 13]], 'date-time': '2023-11-13T00:00:00Z', 'timestamp': 1699833600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 11, 13]], 'date-time': '2023-11-13T00:00:00Z', 'timestamp': 1699833600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [{'DOI': '10.13039/501100009169', 'name': 'Assiut University', 'doi-asserted-by': 'crossref'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2024, 2]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>Nearly four years after its first appearance, and ' 'having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The ' 'purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and ' 'long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential ' 'impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August ' '2023 were selected for this review. The objective of this study was achieved by reviewing, ' 'analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) ' 'observational or randomized clinical trials (RCTs) that support or not the beneficial ' 'clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the ' 'variation in the effects of VD. Articles were collected from electronic databases such as ' 'PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and ' 'Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal ' 'models indicated that VD may act in COVID-19 through protecting the respiratory system by ' 'antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and ' 'adaptive immune functions and up regulation of autophagy gene activity. Our review identified ' '58 clinical studies that met the criteria. The number of publications supporting a beneficial ' 'clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. ' 'Although the total patients included in all articles was 14,071,273, patients included in ' 'publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). ' 'Collectively, extensive observational studies indicated a decisive relationship between low ' 'VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from ' 'intervention studies has demonstrated the effectiveness of VD supplements in treating ' 'COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role ' 'of VD in alleviating symptoms of long COVID-19 disease. However,\xa0eight RCTs and one ' 'meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in ' 'COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic ' 'polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie ' 'the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, ' 'metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by ' 'improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, ' 'evidence has been significantly strengthened over the past 18\xa0months, with several ' 'meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against ' 'COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating ' 'COVID-19 and long COVID-19.</jats:p>', 'DOI': '10.1007/s10787-023-01383-x', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 13]], 'date-time': '2023-11-13T18:01:58Z', 'timestamp': 1699898518000}, 'page': '249-271', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 1, 'title': 'Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm ' 'clinical validation and highlight metformin to improve VDR sensitivity and efficacy', 'prefix': '10.1007', 'volume': '32', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-6462-0917', 'authenticated-orcid': False, 'given': 'Adel A.', 'family': 'Gomaa', 'sequence': 'first', 'affiliation': []}, {'given': 'Yasmin A.', 'family': 'Abdel-Wadood', 'sequence': 'additional', 'affiliation': []}, {'given': 'Romany H.', 'family': 'Thabet', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ghada A.', 'family': 'Gomaa', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 11, 13]]}, 'reference': [ { 'issue': '1', 'key': '1383_CR1', 'doi-asserted-by': 'publisher', 'first-page': '123', 'DOI': '10.1186/s13063-023-07114-5', 'volume': '24', 'author': 'H Abroug', 'year': '2023', 'unstructured': 'Abroug H, Maatouk A, Bennasrallah C, Dhouib W, Ben Fredj M, Zemni I, ' 'Kacem M, Mhalla S et al (2023) Effect of vitamin D supplementation ' 'versus placebo on recovery delay among COVID-19 Tunisian patients: a ' 'randomized-controlled clinical trial. 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