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Vitamin D on COVID-19 Patients During the Pandemic, 2022. A Systematic Review and Meta-Analysis

Asla et al., Current Research in Nutrition and Food Science Journal, doi:10.12944/CRNFSJ.11.1.3
Apr 2023  
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Mortality 36% Improvement Relative Risk Ventilation 30% ICU admission 52% Vitamin D for COVID-19  Asla et al.  META ANALYSIS c19early.org Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
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 79 treatments. c19early.org
Systematic review and meta-analysis of 42 studies with 8,001 COVID-19 patients showing vitamin D deficiency associated with higher mortality, and vitamin D supplementation associated with lower mortality, ICU admission, mechanical ventilation, and length of hospitalization, especially when administered after COVID-19 diagnosis. Doses of 50,000 to 100,000IU showed the greatest benefits for mortality. The Figure 4 caption is incorrectly duplicated from Figure 5.
17 meta analyses show significant improvements with vitamin D treatment for mortality1-12, mechanical ventilation1,6,7,12-14, ICU admission1,3,6,7,10,12-16, hospitalization5,12, severity2,4,6,11,17, and cases8,16,17.
Currently there are 122 vitamin D treatment for COVID-19 studies, showing 36% lower mortality [28‑43%], 19% lower ventilation [-3‑36%], 45% lower ICU admission [28‑58%], 19% lower hospitalization [9‑29%], and 17% fewer cases [9‑24%].
risk of death, 36.0% lower, RR 0.64, p = 0.01.
risk of mechanical ventilation, 30.0% lower, RR 0.70, p < 0.001.
risk of ICU admission, 52.0% lower, RR 0.48, p = 0.02.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Asla et al., 25 Apr 2023, peer-reviewed, 8 authors. Contact: dr_samar11@yahoo.com.
This PaperVitamin DAll
Vitamin D on COVID-19 Patients During the Pandemic, 2022. A Systematic Review and Meta-Analysis
Moamen Mostafa Asla, Asmaa Ahmed Nawar, Esraa Elsayed, Ramadan Abdelmoez Farahat, Ayah Abdulgadir, Mostafa Abdullah Alsharabasy, Sraa Mohamed Elshahawy, Samar A Amer
Current Research in Nutrition and Food Science Journal, doi:10.12944/crnfsj.11.1.3
Numerous connections between the level of vitamin D (Vit-D) and the novel coronavirus disease -19 (COVID-19) have surfaced during the pandemic. So, we conducted this systematic review and meta-analysis to explore the effect of Vit-D deficiency and its supplementation on the clinical outcomes of COVID-19 patients. We looked for relevant articles in Cochrane Library, Scopus, Web Science, PubMed, and EBSCO up until the end of 2022. The Open Meta Analyst software was used to analyze the extracted data. We classified them into two main categories based on their objectives. First, the studies that evaluated the effects of Vit-D deficiency in patients, and lastly, the studies that evaluated Vit-D as a supplement, both on mortality rate, hospitalization duration, ICU admission rate, and mechanical ventilation rate. A total of 8001 COVID-19 patients from 42 studies were included. A high serum Vit-D concentration compared to those with lower levels was associated with a significantly lower mortality rate (RR = 1.5, 95% CI = 1.11: 2.02, p = 0.01). According to the estimated effect of 18 studies, those who took Vit-D supplements had a significantly lower mortality rate, hospitalization duration, ICU admission rate, and mechanical ventilation rate than those who did not. The group receiving Vit-D doses
Authors Contributions The manuscript has been read and approved by all the authors, that the requirements for authorship have been met, and that each author has substantial contributions to each of the three components mentioned below: 1. Concept and design of study or acquisition of data or analysis and interpretation of data. 2. Drafting the article or revising it critically for important intellectual content, and 3. Final approval of the version to be published. Conflicts of interests The authors have declared no conflicts of interest.
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Bmj. 2003;327:557-60.', 'DOI': '10.1136/bmj.327.7414.557'}, { 'key': 'ref19', 'doi-asserted-by': 'publisher', 'unstructured': '20.\tCastillo ME, Costa LME, Barrios JMV, Díaz JFA, Miranda JL, Bouillon ' 'R, et al. Effect of calcifediol treatment and best available therapy ' 'versus best available therapy on intensive care unit admission and ' 'mortality among patients hospitalized for COVID-19: A pilot randomized ' 'clinical study. The Journal of steroid biochemistry and molecular ' 'biology. 2020;203:105751.', 'DOI': '10.1016/j.jsbmb.2020.105751'}, { 'key': 'ref20', 'doi-asserted-by': 'publisher', 'unstructured': '21.\tMariani J, Antonietti L, Tajer C, Ferder L, Inserra F, Cunto MS, et ' 'al. High-dose vitamin D versus placebo to prevent complications in ' 'COVID-19 patients: Multicentre randomized controlled clinical trial. ' 'PLoS ONE. 2022;17:1-16.', 'DOI': '10.1186/s13063-021-05073-3'}, { 'key': 'ref21', 'doi-asserted-by': 'publisher', 'unstructured': '22.\tMurai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, ' 'et al. Effect of a single high dose of vitamin D3 on hospital length of ' 'stay in patients with moderate to severe COVID-19: a randomized clinical ' 'trial. Jama. 2021;325:1053-60.', 'DOI': '10.1001/jama.2020.26848'}, { 'key': 'ref22', 'doi-asserted-by': 'publisher', 'unstructured': '23.\tDe Niet S, Trémège M, Coffiner M, Rousseau A-F, Calmes D, Frix A-N, ' 'et al. Positive effects of vitamin D supplementation in patients ' 'hospitalized for COVID-19: a randomized, double-blind, ' 'placebo-controlled trial. Nutrients. 2022;14:3048.', 'DOI': '10.3390/nu14153048'}, { 'key': 'ref23', 'doi-asserted-by': 'crossref', 'unstructured': '24.\tTorres M, Casado G, Vigón L, Rodríguez-Mora S, Mateos E, ' 'Ramos-Martín F, et al. Changes in the immune response against SARS-CoV-2 ' 'in individuals with severe COVID-19 treated with high dose of vitamin D. ' 'Biomedicine & Pharmacotherapy. 2022;150:112965.', 'DOI': '10.1016/j.biopha.2022.112965'}, { 'key': 'ref24', 'doi-asserted-by': 'publisher', 'unstructured': '25.\tCannata-Andía JB, Díaz-Sottolano A, Fernández P, Palomo-Antequera ' 'C, Herrero-Puente P, Mouzo R, et al. A single-oral bolus of 100,000 IU ' 'of cholecalciferol at hospital admission did not improve outcomes in the ' 'COVID-19 disease: the COVID-VIT-D—a randomised multicentre international ' 'clinical trial. BMC medicine. 2022;20:1-13.', 'DOI': '10.1186/s12916-022-02290-8'}, { 'key': 'ref25', 'doi-asserted-by': 'crossref', 'unstructured': '26.\tAnnweiler C, Beaudenon M, Gautier J, Gonsard J, Boucher S, Chapelet ' 'G, et al. High-dose versus standard-dose vitamin D supplementation in ' 'older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, ' 'randomized controlled superiority trial. PLoS Medicine. 2022;19:1-18.', 'DOI': '10.1371/journal.pmed.1003999'}, { 'key': 'ref26', 'doi-asserted-by': 'publisher', 'unstructured': '27.\tLakkireddy M, Gadiga SG, Malathi RD, Karra ML, Raju ISSVPM, Ragini, ' 'et al. Impact of daily high dose oral vitamin D therapy on the ' 'inflammatory markers in patients with COVID 19 disease. Scientific ' 'Reports. 2021;11:1-8.', 'DOI': '10.1038/s41598-021-97181-y'}, { 'key': 'ref27', 'doi-asserted-by': 'publisher', 'unstructured': '28.\tSoliman AR, Abdelaziz TS, Fathy A. Impact of Vitamin D Therapy on ' 'the Progress COVID-19: Six Weeks Follow-Up Study of Vitamin D Deficient ' 'Elderly Diabetes Patients. Proceedings of Singapore Healthcare. ' '2021;0:1-5.', 'DOI': '10.1177/20101058211041405'}, { 'key': 'ref28', 'doi-asserted-by': 'publisher', 'unstructured': '29.\tRastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, ' 'et al. 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American Journal of Clinical ' 'Nutrition. 2021;114:598-604.', 'DOI': '10.1093/ajcn/nqab227'}, { 'key': 'ref34', 'doi-asserted-by': 'publisher', 'unstructured': '35.\tVassiliou AG, Jahaj E, Pratikaki M, Keskinidou C, Detsika M, ' 'Grigoriou E, et al. Vitamin D deficiency correlates with a reduced ' 'number of natural killer cells in intensive care unit (ICU) and non-ICU ' 'patients with COVID-19 pneumonia. Hellenic Journal of Cardiology. ' '2021;62:381.', 'DOI': '10.1016/j.hjc.2020.11.011'}, { 'key': 'ref35', 'doi-asserted-by': 'publisher', 'unstructured': '36.\tNogues X, Ovejero D, Pineda-Moncusí M, Bouillon R, Arenas D, ' 'Pascual J, et al. Calcifediol treatment and COVID-19–related outcomes. ' 'The Journal of Clinical Endocrinology & Metabolism. 2021;106:e4017-27.', 'DOI': '10.1210/clinem/dgab405'}, { 'key': 'ref36', 'doi-asserted-by': 'publisher', 'unstructured': '37.\tCampi I, Gennari L, Merlotti D, Mingiano C, Frosali A, Giovanelli ' 'L, et al. Vitamin D and COVID-19 severity and related mortality: a ' 'prospective study in Italy. BMC Infectious Diseases. 2021;21:1-13.', 'DOI': '10.1186/s12879-021-06281-7'}, { 'key': 'ref37', 'doi-asserted-by': 'publisher', 'unstructured': '38.\tDemir M, Demir F, Aygun H. Vitamin D deficiency is associated with ' 'COVID-19 positivity and severity of the disease. Journal of Medical ' 'Virology. 2021;93:2992-9.', 'DOI': '10.1002/jmv.26832'}, { 'key': 'ref38', 'doi-asserted-by': 'publisher', 'unstructured': '39.\tRadujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, ' 'Merle U. Vitamin D deficiency and outcome of COVID-19 patients. ' 'Nutrients. 2020;12:2757.', 'DOI': '10.3390/nu12092757'}, { 'key': 'ref39', 'doi-asserted-by': 'publisher', 'unstructured': '40.\tMariani J, Giménez VMM, Bergam I, Tajer C, Antonietti L, Inserra F, ' 'et al. Association between vitamin D deficiency and COVID-19 incidence, ' 'complications, and mortality in 46 countries: an ecological study. 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' 'European journal of endocrinology. 2020;183:R133-47.', 'DOI': '10.1530/eje-20-0665'}, { 'key': 'ref52', 'doi-asserted-by': 'publisher', 'unstructured': '53.\tMalek Mahdavi A. A brief review of interplay between vitamin D and ' 'angiotensin‐converting enzyme 2: Implications for a potential treatment ' 'for COVID‐19. Reviews in medical virology. 2020;30:e2119.', 'DOI': '10.1002/rmv.2119'}, { 'key': 'ref53', 'doi-asserted-by': 'publisher', 'unstructured': '54.\tPal R, Bhansali A. COVID-19, diabetes mellitus and ACE2: the ' 'conundrum. Diabetes research and clinical practice. 2020;162.', 'DOI': '10.1016/j.diabres.2020.108132'}, { 'key': 'ref54', 'doi-asserted-by': 'publisher', 'unstructured': '55.\tZou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, et al. ' 'Angiotensin-converting enzyme 2 protects from lethal avian influenza A ' 'H5N1 infections. Nature communications. 2014;5:1-7.', 'DOI': '10.1038/ncomms4594'}, { 'key': 'ref55', 'doi-asserted-by': 'publisher', 'unstructured': '56.\tBaktash V, Hosack T, Patel N, Shah S, Kandiah P, Van den Abbeele K, ' 'et al. Vitamin D status and outcomes for hospitalised older patients ' 'with COVID-19. Postgraduate medical journal. 2021;97:442-7.', 'DOI': '10.1136/postgradmedj-2020-138712'}, { 'key': 'ref56', 'doi-asserted-by': 'publisher', 'unstructured': '57.\tGiannini S, Passeri G, Tripepi G, Sella S, Fusaro M, Arcidiacono G, ' 'et al. Effectiveness of in-hospital cholecalciferol use on clinical ' 'outcomes in comorbid COVID-19 patients: a hypothesis-generating study. ' 'Nutrients. 2021;13:219.', 'DOI': '10.3390/nu13010219'}, { 'key': 'ref57', 'doi-asserted-by': 'publisher', 'unstructured': '58.\tLing SF, Broad E, Murphy R, Pappachan JM, Pardesi-Newton S, Kong ' 'M-F, et al. 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Nutrients. 2020;12:3377.', 'DOI': '10.3390/nu12113377'}, { 'key': 'ref60', 'doi-asserted-by': 'publisher', 'unstructured': '61.\tCereda E, Bogliolo L, Lobascio F, Barichella M, Zecchinelli AL, ' 'Pezzoli G, et al. Vitamin D supplementation and outcomes in coronavirus ' 'disease 2019 (COVID-19) patients from the outbreak area of Lombardy, ' 'Italy. Nutrition (Burbank, Los Angeles County, Calif). 2021;82:111055.', 'DOI': '10.1016/j.nut.2020.111055'}, { 'key': 'ref61', 'doi-asserted-by': 'publisher', 'unstructured': '62.\tMaghbooli Z, Sahraian MA, Ebrahimi M, Pazoki M, Kafan S, Tabriz HM, ' 'et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ' 'ng/mL reduced risk for adverse clinical outcomes in patients with ' 'COVID-19 infection. PloS one. 2020;15:e0239799.', 'DOI': '10.1371/journal.pone.0239799'}, { 'key': 'ref62', 'doi-asserted-by': 'publisher', 'unstructured': '63.\tGriffin G, Hewison M, Hopkin J, Kenny RA, Quinton R, Rhodes J, et ' 'al. Perspective: Vitamin D supplementation prevents rickets and acute ' 'respiratory infections when given as daily maintenance but not as ' 'intermittent bolus: implications for COVID-19. Clinical Medicine. ' '2021;21:e144.', 'DOI': '10.7861/clinmed.2021-0035'}, { 'key': 'ref63', 'doi-asserted-by': 'publisher', 'unstructured': '64.\tKetha H, Thacher TD, Oberhelman SS, Fischer PR, Singh RJ, Kumar R. ' 'Comparison of the effect of daily versus bolus dose maternal vitamin D3 ' 'supplementation on the 24, 25-dihydroxyvitamin D3 to 25-hydroxyvitamin ' 'D3 ratio. Bone. 2018;110:321-5.', 'DOI': '10.1016/j.bone.2018.02.024'}, { 'key': 'ref64', 'doi-asserted-by': 'publisher', 'unstructured': '65.\tJolliffe DA, Camargo Jr CA, Sluyter JD, Aglipay M, Aloia JF, Ganmaa ' 'D, et al. Vitamin D supplementation to prevent acute respiratory ' 'infections: a systematic review and meta-analysis of aggregate data from ' 'randomised controlled trials. The lancet Diabetes & endocrinology. ' '2021;9:276-92.', 'DOI': '10.1136/thorax-2020-btsabstracts.105'}, { 'key': 'ref65', 'doi-asserted-by': 'publisher', 'unstructured': '66.\tIversen HH, Bjertnæs ØA, Skudal KE. Patient evaluation of hospital ' 'outcomes: an analysis of open-ended comments from extreme clusters in a ' 'national survey. BMJ open. 2014;4:e004848.', 'DOI': '10.1136/bmjopen-2014-004848'}, { 'key': 'ref66', 'doi-asserted-by': 'publisher', 'unstructured': '67.\tBinkley N, Ramamurthy R, Krueger D. Low vitamin D status: ' 'definition, prevalence, consequences, and correction. Endocrinology and ' 'Metabolism Clinics. 2010;39:287-301.', 'DOI': '10.1016/j.ecl.2010.02.008'}, { 'key': 'ref67', 'doi-asserted-by': 'publisher', 'unstructured': '68.\tRake C, Gilham C, Bukasa L, Ostler R, Newton M, Wild JP, et al. ' 'High-dose oral vitamin D supplementation and mortality in people aged ' '65-84 years: the VIDAL cluster feasibility RCT of open versus ' 'double-blind individual randomisation. 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Reviews in Endocrine and Metabolic ' 'Disorders. 2021:1-5.', 'DOI': '10.1007/s11154-021-09683-9'}], 'container-title': 'Current Research in Nutrition and Food Science Journal', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.foodandnutritionjournal.org/volume11number1/vitamin-d-on-covid-19-patients-during-the-pandemic-2022-a-systematic-review-and-meta-analysis/', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 4, 27]], 'date-time': '2023-04-27T08:02:59Z', 'timestamp': 1682582579000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://www.foodandnutritionjournal.org/volume11number1/vitamin-d-on-covid-19-patients-during-the-pandemic-2022-a-systematic-review-and-meta-analysis/'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 4, 25]]}, 'references-count': 69, 'journal-issue': { 'issue': '1', 'published-online': {'date-parts': [[2023, 4, 25]]}, 'published-print': {'date-parts': [[2023, 4, 25]]}}, 'URL': 'http://dx.doi.org/10.12944/CRNFSJ.11.1.3', 'relation': {}, 'ISSN': ['2322-0007', '2347-467X'], 'subject': [], 'container-title-short': 'Curr Res Nutr Food Sci', 'published': {'date-parts': [[2023, 4, 25]]}, 'assertion': [ { 'value': '2023-4-25', 'order': 0, 'name': 'published_print', 'label': 'Published Print', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
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