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All Studies   Meta Analysis    Recent:   

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

Gomaa et al., Inflammopharmacology, doi:10.1007/s10787-023-01383-x
Nov 2023  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 81 treatments. c19early.org
Review of 58 studies with 14,071,273 patients showing a beneficial effect of vitamin D supplementation in COVID-19 and long COVID. 49 studies (86%) with 14,029,411 patients (99.7%) found vitamin D effective, including 12 meta-analyses. Observational studies showed an inverse relationship between vitamin D levels and COVID-19 severity and mortality. RCTs demonstrated efficacy of vitamin D, especially with early administration of high-dose supplements. Genetic polymorphisms and impaired receptor signaling may underlie variability in vitamin D effects. Authors highlight metformin as potentially improving vitamin D receptor sensitivity and efficacy.
Reviews covering vitamin D for COVID-19 include1-28.
Review covers vitamin D and metformin.
Gomaa et al., 13 Nov 2023, peer-reviewed, 4 authors, study period January 2022 - August 2023. Contact: a.gomma@aun.edu.eg.
This PaperVitamin DAll
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
Adel A Gomaa, Yasmin A Abdel-Wadood, Romany H Thabet, Ghada A Gomaa
Inflammopharmacology, doi:10.1007/s10787-023-01383-x
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, eight 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 months, 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.
Author contributions AAG: resources, writing-original draft, writing-review and editing, supervision. YAA-W: resources, review and editing. RHT: review and editing; GAG: review and editing. Funding Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). This study was not funded by any specific grant from funding agencies in the public, commercial, or not for-profit sectors. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. Availability of data and materials Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/...
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{ '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. Trials 24(1):123. ' 'https://doi.org/10.1186/s13063-023-07114-5. (PMID: 36803273; PMCID: ' 'PMC9940050)', 'journal-title': 'Trials'}, { 'issue': '12', 'key': '1383_CR2', 'doi-asserted-by': 'publisher', 'first-page': '2346', 'DOI': '10.3390/genes13122346', 'volume': '13', 'author': 'WHM Albu-Mohammed', 'year': '2022', 'unstructured': 'Albu-Mohammed WHM, Anvari E, Fateh A (2022) Evaluating the role of BglI ' 'rs739837 and TaqI rs731236 polymorphisms in Vitamin D receptor with ' 'SARS-CoV-2 variants mortality rate. Genes 13(12):2346. ' 'https://doi.org/10.3390/genes13122346. 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(PMID:37629143;PMCID:PMC10454552)', 'journal-title': 'Int J Mol Sci'}, { 'key': '1383_CR22', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S1473-3099(23)00299-2', 'author': 'CT Bramante', 'year': '2023', 'unstructured': 'Bramante CT, Buse JB, Liebovitz DM, Nicklas JM, Puskarich MA, Cohen K, ' 'Belani HK et al (2023) Outpatient treatment of COVID-19 and incidence of ' 'post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, ' 'randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet ' 'Infect Dis. https://doi.org/10.1016/S1473-3099(23)00299-2', 'journal-title': 'Lancet Infect Dis'}, { 'key': '1383_CR23', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fpubh.2022.888168', 'volume': '10', 'author': 'D Briceno Noriega', 'year': '2022', 'unstructured': 'Briceno Noriega D, Savelkoul HFJ (2022) Vitamin D: a potential ' 'mitigation tool for the endemic stage of the COVID-19 pandemic? 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