The Role of Vitamin D in COVID-19 Survival and Prevention: A Meta-analysis
Shamina Begum, Hyder Osman Mirghani, Prof Elmalaika Nazik, Seid Ahmed Obaid, MD, M.Sc Husain
doi:10.18502/sjms.v19i1.15776
Background: COVID-19 is still ongoing with frequently discovered new strains, although vaccines are highly effective for prevention. Literature on vitamin D supplementation in COVID-19 prevention and its effect on survival is scarce. This meta-analysis assessed the role of vitamin D supplementation in COVID-19 prevention and survival. Methods: Four databases (Web of Science, SCOPUS, PubMed, MEDLINE, and the first 100 articles of Google Scholar) were searched for articles published up to September 2023. The keywords used were COVID-19, mortality, vitamin D supplementation, calcitriol, cholecalciferol, Calcifediol, survival, death, and prevention. Six hundred and seven studies were retrieved, and four hundred and three remained after duplication removal; of them eighty-three full texts were screened, and of them, only sixteen (prospective, randomized controlled trials, and retrospective studies) were included in the final meta-analysis. Results: Sixteen observational studies including 5905,109 patients and 186,500 events were included. Vitamin D supplementation reduced mortality among patients with odd ratio, 2.31, 95% CI,; in addition, supplementation was effective in COVID-19 prevention, odd ratio, 1.92, 95% CI, 1.01-3.64. Conclusion: Vitamin D supplementation prevented COVID-19 and increased survival among patients admitted with moderate/severe COVID-19.
Ethical Considerations The authors did not include any manuscript published by them.
Competing Interests None
References
Alcala-Diaz, Limia-Perez, Gomez-Huelgas, Martin-Escalante, Cortes-Rodriguez et al., Calcifediol treatment and hospital mortality due to COVID-19: A cohort study, Nutrients,
doi:10.3390/nu13061760
Alcalá-Santiago, Rodríguez-Barranco, Rava, Jiménez-Sousa, Gil et al., Vitamin D deficiency and COVID-19: A biological database study on pathways and gene-disease associations, International Journal of Molecular Sciences,
doi:10.3390/ijms232214256
Annweiler, Beaudenon, Gautier, Gonsard, Boucher et al., Highdose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial, PLoS Medicine,
doi:10.1371/journal.pmed.1003999
Annweiler, Corvaisier, Gautier, Dubée, Legrand et al., Vitamin D supplementation associated to better survival in hospitalized frail elderly COVID-19 patients: The GERIA-COVID quasi-experimental study, Nutrients,
doi:10.3390/nu12113377
Annweiler, Hanotte, Grandin De L'eprevier, Sabatier, Lafaie et al., Vitamin D and survival in COVID-19 patients: A quasi-experimental study, The Journal of Steroid Biochemistry and Molecular Biology,
doi:10.1016/j.jsbmb.2020.105771
Bassatne, Basbous, Chakhtoura, El Zein, Rahme et al., The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis, Metabolism: Clinical and Experimental,
doi:10.1016/j.metabol.2021.154753
Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., Mechanisms in endocrinology: Vitamin D and COVID-19, European Journal of Endocrinology,
doi:10.1530/EJE-20-0665
Brunvoll, Nygaard, Ellingjord-Dale, Holland, Istre et al., Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: Sudan Journal of Medical Sciences Begum, Mirghani Quadruple blinded, randomised placebo controlled trial, BMJ (Clinical Research Ed,
doi:10.1136/bmj-2022-071245
Butler-Laporte, Nakanishi, Mooser, Morrison, Abdullah et al., Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study, PLoS Medicine,
doi:10.1371/journal.pmed.1003605
Cangiano, Fatti, Danesi, Gazzano, Croci et al., Mortality in an Italian nursing home during COVID-19 pandemic: Correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests, Aging,
doi:10.18632/aging.202307
Cannata-Andía, Díaz-Sottolano, Fernández, Palomo-Antequera, Herrero-Puente et al., COVID-VIT-D trial collaborators. 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,
doi:10.1186/s12916-022-02290-8
Castillo, Entrenas Costa, Vaquero Barrios, Alcalá Díaz, López Miranda 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, The Journal of Steroid Biochemistry and Molecular Biology,
doi:10.1016/j.jsbmb.2020.105751
Cereda, Bogliolo, Lobascio, Barichella, Zecchinelli et al., Vitamin D supplementation and outcomes in coronavirus disease 2019 (COVID-19) patients from the outbreak area of Lombardy, Italy. Nutrition,
doi:10.1016/j.nut.2020.111055
Chen, Haupert, Zimmermann, Shi, Fritsche et al., Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: A meta-analysis and systematic review, The Journal of Infectious Diseases,
doi:10.1093/infdis/jiac136
D'avolio, Avataneo, Manca, Cusato, De Nicolò et al., 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359
Dirks, Ackermans, Lips, De Jongh, Vervloet et al., The when, what & how of measuring vitamin D metabolism in clinical medicine, Nutrients,
doi:10.3390/nu10040482
Feentved Ødum, Kongsbak-Wismann, Vitamin D and SARS-CoV-2, Basic & Clinical Pharmacology & Toxicology,
doi:10.1111/bcpt.13872
Fernandes, Murai, Reis, Sales, Santos et al., Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19, The American Journal of Clinical Nutrition,
doi:10.1093/ajcn/nqab426
Gharibi, Babaloo, Hosseini, Abdollahpour-Alitappeh, Hashemi et al., Targeting STAT3 in cancer and autoimmune diseases, European Journal of Pharmacology,
doi:10.1016/j.ejphar.2020.173107
Giannini, Passeri, Tripepi, Sella, Fusaro et al., Effectiveness of in-hospital cholecalciferol use on clinical outcomes in comorbid COVID-19 patients: A hypothesis-generating study, Nutrients,
doi:10.3390/nu13010219
Griffin, Hewison, Hopkin, Kenny, Quinton 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,
doi:10.7861/clinmed.2021-0035
Hartling, Milne, Hamm, Vandermeer, Ansari et al., Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers, Journal of Clinical Epidemiology,
doi:10.1016/j.jclinepi.2013.03.003
Hernández, Nan, Fernandez-Ayala, García-Unzueta, Hernández-Hernández et al., Vitamin D status in hospitalized patients with SARS-CoV-2 infection, The Journal of Clinical Endocrinology and Metabolism,
doi:10.1210/clinem/dgaa733
Hosseini, El Abd, Ducharme, Effects of vitamin D supplementation on COVID-19 related outcomes: A systematic review and meta-analysis, Nutrients,
doi:10.3390/nu14102134
Hu, Kung, Cave, Banh, Effects of vitamin D serum level on morbidity and mortality in patients with COVID-19: A systematic review and meta-analysis, Journal of Pharmacy & Pharmaceutical Sciences,
doi:10.18433/jpps32590
Igelström, Campbell, Craig, Katikireddi, Cochrane's risk of bias tool for non-randomized studies (ROBINS-I) is frequently misapplied: A methodological systematic review, Journal of Clinical Epidemiology,
doi:10.1016/j.jclinepi.2021.08.022
Jolliffe, Camargo, Jr, Sluyter, Aglipay et al., Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials, medRxiv,
doi:10.1101/2020.07.14.20152728
Jolliffe, Holt, Greenig, Talaei, Perdek et al., Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: Phase 3 randomised controlled trial (CORONAVIT), BMJ (Clinical Research Ed,
doi:10.1136/bmj-2022-071230
Karonova, Chernikova, Golovatyuk, Bykova, Grant et al., Vitamin D intake may reduce SARS-CoV-2 infection morbidity in health care workers, Nutrients,
doi:10.3390/nu14030505
Kouhpayeh, Shariati, Boshtam, Rahimmanesh, Mirian et al., The molecular basis of COVID-19 pathogenesis, conventional and nanomedicine therapy, International Journal of Molecular Sciences,
doi:10.3390/ijms22115438
Ling, Broad, Murphy, Pappachan, Pardesi-Newton et al., High-dose cholecalciferol booster therapy is associated with a reduced risk of mortality in patients with COVID-19: A cross-sectional multicentre observational study, Nutrients,
doi:10.3390/nu12123799
Ma, Zhou, Heianza, Qi, Habitual use of vitamin D supplements and risk of coronavirus disease 2019 (COVID-19) infection: A prospective study in UK Biobank, The American Journal of Clinical Nutrition,
doi:10.1093/ajcn/nqaa381
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data, BMJ (Clinical Research Ed,
doi:10.1136/bmj.i6583
Meltzer, Best, Zhang, Vokes, Arora et al., Association of vitamin D status and other clinical characteristics with COVID-19 test results, JAMA Network Open,
doi:10.1001/jamanetworkopen.2020.19722
Murai, Fernandes, Sales, Pinto, Goessler 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, Journal of the American Medical Association,
doi:10.1001/jama.2020.26848
Nguyen, Raju, Da Graca, Wang, Mohamed et al., 25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients, PLoS One,
doi:10.1371/journal.pone.0268038
Nikniaz, Akbarzadeh, Hosseinifard, Hosseini, The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis, MedRxiv,
doi:10.1101/2021.01.04.21249219
Nogues, Ovejero, Pineda-Moncusí, Bouillon, Arenas et al., Calcifediol treatment and COVID-19-related outcomes, The Journal of Clinical Endocrinology and Metabolism,
doi:10.1210/clinem/dgab405
Oristrell, Oliva, Subirana, Casado, Domínguez et al., Association of calcitriol supplementation with reduced COVID-19 mortality in patients with chronic kidney disease: A populationbased study, Biomedicines,
doi:10.3390/biomedicines9050509
Pal, Banerjee, Bhadada, Shetty, Singh et al., Vitamin D supplementation and clinical outcomes in COVID-19: A systematic review and meta-analysis, Journal of Endocrinological Investigation,
doi:10.1007/s40618-021-01614-4
Quesada-Gomez, Entrenas-Castillo, Bouillon, Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166, The Journal of Steroid Biochemistry and Molecular Biology,
doi:10.1016/j.jsbmb.2020.105719
Rawat, Roy, Maitra, Shankar, Khanna et al., Vitamin D supplementation and COVID-19 treatment: A systematic review and meta-analysis, Diabetes & Metabolic Syndrome,
doi:10.1016/j.dsx.2021.102189
Shah, Saxena, Mavalankar, Vitamin D supplementation, COVID-19 and disease severity: A meta-analysis, QJM,
doi:10.1093/qjmed/hcab009
Silva, Lazaretti-Castro, Vitamin D metabolism and extraskeletal outcomes: An update, Archives of Endocrinology and Metabolism,
doi:10.20945/2359-3997000000565
Tomaszewska, Rustecka, Lipińska-Opałka, Piprek, Kloc et al., The role of vitamin D in COVID-19 and the impact of pandemic restrictions on vitamin D blood content, Frontiers in Pharmacology,
doi:10.3389/fphar.2022.836738
Villasis-Keever, López-Alarcón, Miranda-Novales, Zurita-Cruz, Barrada-Vázquez et al., Efficacy and safety of vitamin D supplementation to prevent COVID-19 in frontline healthcare workers. A randomized clinical trial, Archives of Medical Research,
doi:10.1016/j.arcmed.2022.04.003
Wang, Paulson, Pease, Watson, Comfort et al., Estimating excess mortality due to the COVID-19 pandemic: A systematic analysis of COVID-19related mortality, 2020-21, Lancet,
doi:10.1016/S0140-6736(21)02796-3