Vitamin D, acute respiratory infections, and Covid-19: the curse of small-size randomised trials. A critical review with meta-analysis of randomised trials
Philippe Autier, Giulia Doi, Patrick Mullie, Patrick Vankrunkelsven, Oriana D’ecclesiis, Sara Gandini
doi:10.1101/2024.04.26.24306354
Background: Randomised trials conducted before 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, these health benefits were not confirmed by larger randomised trials published after 2021. Objective: To examine the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and on VDS for the prevention of ARI. Method: A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al., 2021. The associations between VDS vs no VDS, and admission to ICU were evaluated using random effect models. Meta-analyses were done for all trials and by groups trial size. Publication bias was assessed using the LFK index (no bias if index between -1 and +1) and the Trim and Fill method. Results: Nine trials on VDS for preventing admission to ICU were identified. The summary odds ratio (SOR) was 0.61 (95%CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (effect modification: p=0.04). The LFK index was -3.79, and after Trim and Fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (effect modification p=0.0001). The LFK index was -3.11, and after Trim and Fill, the SOR was 0.96 (0.88-1.05). Conclusion: Strong publication bias affected randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of smallsize randomised trials that generally exaggerate health benefits.
References
Abroug, Maatouk, Bennasrallah, Dhouib, Fredj et al., Effect of vitamin D supplementation versus placebo on recovery delay among COVID-19 Tunisian patients: a randomizedcontrolled clinical trial, Trials,
doi:10.1186/s13063-023-07114-5Amin, Drenos, No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data, BMJ Nutr Prev Health,
doi:10.1136/bmjnph-2020-000151Amrein, Schnedl, Holl, Riedl, Christopher et al., Effect of high-dose vitamin D3on hospital length of stay in critically ill patients with vitamin D deficiency: The VITdAL-ICU randomized clinical trial, JAMA -Journal of the American Medical Association,
doi:10.1001/jama.2014.13204Annweiler, Beaudenon, Gautier, Gonsard, Boucher 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 Med,
doi:10.1371/journal.pmed.1003999Antonelli, Kushner, Low Serum Levels of 25-Hydroxyvitamin D Accompany Severe COVID-19 Because it is a Negative Acute Phase Reactant, Am J Med Sci,
doi:10.1016/j.amjms.2021.06.005Autier, Mullie, Macacu, Dragomir, Boniol et al., Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials, The Lancet Diabetes & Endocrinology,
doi:10.1016/s2213-8587(17)30357-1Bergman, The link between vitamin D and COVID-19: distinguishing facts from fiction, J Intern Med,
doi:10.1111/joim.13158Binkley, Coursin, Krueger, Iglar, Heiner et al., Surgery alters parameters of vitamin D status and other laboratory results, Osteoporos Int,
doi:10.1007/s00198-016-3819-9Bishop, Ashfaq, Melnick, Vazquez-Escarpanter, Fialkow et al., REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients, Nutrition,
doi:10.1016/j.nut.2022.111899Borenstein, Common mistakes in meta-analysis
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: quadruple blinded, randomised placebo controlled trial, Bmj,
doi:10.1136/bmj-2022-071245Butler-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 Med,
doi:10.1371/journal.pmed.1003605Cannata-Andia, Diaz-Sottolano, Fernandez, Palomo-Antequera, Herrero-Puente 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 Med,
doi:10.1186/s12916-022-02290-8Castillo, Costa, Barrios, Díaz, 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: A pilot randomized clinical study, J Steroid Biochem Mol Biol,
doi:10.1016/j.jsbmb.2020.105751Cervero, López-Wolf, Casado, Mena, Ryan-Murua et al., Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D(3) in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial, Front Pharmacol,
doi:10.3389/fphar.2022.863587Chauss, Freiwald, Mcgregor, Yan, Wang et al., Autocrine vitamin D signaling switches off pro-inflammatory programs of T(H)1 cells, Nat Immunol,
doi:10.1038/s41590-021-01080-3Cornell, Mulrow, Localio, Stack, Meibohm et al., Random-effects metaanalysis of inconsistent effects: a time for change, Ann Intern Med,
doi:10.7326/M13-2886Cui, Tian, Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study, J Transl Med,
doi:10.1186/s12967-021-02973-5D'ecclesiis, Gavioli, Martinoli, Raimondi, Chiocca et al., Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis, PLoS One,
doi:10.1371/journal.pone.0268396Dissanayake, Silva, Sumanatilleke, De Silva, Gamage et al., Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgab892Elamir, Amir, Lim, Rana, Lopez et al., A randomized pilot study using calcitriol in hospitalized COVID-19 patients, Bone,
doi:10.1016/j.bone.2021.116175Furuya-Kanamori, Barendregt, Doi, A new improved graphical and quantitative method for detecting bias in meta-analysis, Int J Evid Based Healthc,
doi:10.1097/XEB.0000000000000141Ginde, Brower, Caterino, Finck, Banner-Goodspeed et al., Early High-Dose Vitamin D(3) for Critically Ill, Vitamin D-Deficient Patients, N Engl J Med,
doi:10.1056/NEJMoa1911124Hopefl, Ben-Eltriki, Association Between Vitamin D Levels and Inflammatory Markers in COVID-19 Patients: A Meta-Analysis of Observational Studies, J Pharm Pharm Sci,
doi:10.18433/jpps32518Ioannidis, Greenland, Hlatky, Khoury, Macleod et al., Increasing value and reducing waste in research design, conduct, and analysis, Lancet,
doi:10.1016/s0140-6736(13)62227-8Jevalikar, Mithal, Singh, Sharma, Farooqui et al., Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19, Sci Rep,
doi:10.1038/s41598-021-85809-yJolliffe, Camargo, Sluyter, Aglipay, Aloia et al., Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00051-6Jolliffe, 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,
doi:10.1136/bmj-2022-071230Karonova, Golovatyuk, Kudryavtsev, Chernikova, Mikhaylova et al., Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study, Nutrients,
doi:10.3390/nu14132602Kummel, Krumbein, Fragkou, Hunerbein, Reiter et al., Vitamin D supplementation for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials, Front Immunol,
doi:10.3389/fimmu.2022.1023903Lakkireddy, Gadiga, Malathi, Karra, Raju et al., Effect of Short Term High Dose Oral Vitamin D Therapy on the Inflammatory Markers in Patients with COVID 19 Disease, Archives of Clinical and Biomedical Research,
doi:10.26502/acbr.50170273Langan, Higgins, Jackson, Bowden, Veroniki et al., A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses, Res Synth Methods,
doi:10.1002/jrsm.1316Li, Van Geffen, Van Weele, Zhang, He et al., An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank, Sci Rep,
doi:10.1038/s41598-021-97679-5Li-Ng, Aloia, Pollack, Cunha, Mikhail et al., A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections, Epidemiol Infect,
doi:10.1017/S0950268809002404Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science,
doi:10.1126/science.1123933Looker, Serum 25-hydroxyvitamin D and risk of major osteoporotic fractures in older U.S. adults, J Bone Miner Res,
doi:10.1002/jbmr.1828Lopez, Fah, Woetmann, Ødum, Bonefeld et al., Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses, Front Immunol,
doi:10.3389/fimmu.2021.722806Ma, Zhou, Heianza, Qi, Habitual use of vitamin D supplements and risk of coronavirus disease 2019 (COVID-19) infection: a prospective study in UK Biobank, Am J Clin Nutr,
doi:10.1093/ajcn/nqaa381Maghbooli, Sahraian, Jamalimoghadamsiahkali, Asadi, Zarei et al., Treatment With 25-Hydroxyvitamin D(3) (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial, Endocr Pract,
doi:10.1016/j.eprac.2021.09.016Mariani, Antonietti, Tajer, Ferder, Inserra et al., High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial, PLoS One,
doi:10.1371/journal.pone.0267918Martineau, Vitamin D in the prevention or treatment of COVID-19, Proc Nutr Soc
Murai, Fernandes, Antonangelo, Gualano, Pereira, Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19, Clinics,
doi:10.6061/clinics/2021/e3549Niet, Trémège, Coffiner, Rousseau, Calmes et al., Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial, Nutrients,
doi:10.3390/nu14153048Nogues, Ovejero, Pineda-Moncusí, Bouillon, Arenas et al., Calcifediol Treatment and COVID-19-Related Outcomes, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgab405Patchen, Clark, Gaddis, Hancock, Cassano, Genetically predicted serum vitamin D and COVID-19: a Mendelian randomisation study, BMJ Nutr Prev Health,
doi:10.1136/bmjnph-2021-000255Pham, Rahman, Majidi, Waterhouse, Neale, Acute Respiratory Tract Infection and 25-Hydroxyvitamin D Concentration: A Systematic Review and Meta-Analysis, Int J Environ Res Public Health,
doi:10.3390/ijerph16173020Pittas, Hughes, Sheehan, Ware, Knowler et al., Vitamin D Supplementation and Prevention of Type 2 Diabetes, N Engl J Med,
doi:10.1056/NEJMoa1900906Rastogi, Bhansali, Khare, Suri, Yaddanapudi et al., Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study), Postgrad Med J,
doi:10.1136/postgradmedj-2020-139065Sabico, Enani, Sheshah, Aljohani, Aldisi et al., Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial, Nutrients,
doi:10.3390/nu13072170Sanchez-Zuno, Gonzalez-Estevez, Matuz-Flores, Macedo-Ojeda, Hernandez-Bello et al., Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation, J Clin Med,
doi:10.3390/jcm10112378Schwab, Kreiliger, Held, Assessing treatment effects and publication bias across different specialties in medicine: a meta-epidemiological study, BMJ Open,
doi:10.1136/bmjopen-2020-045942Scragg, Stewart, Waayer, Lawes, Toop et al., Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial, JAMA Cardiol,
doi:10.1001/jamacardio.2017.0175Sjoding, Luo, Miller, Iwashyna, When do confounding by indication and inadequate risk adjustment bias critical care studies? A simulation study, Crit Care,
doi:10.1186/s13054-015-0923-8Smaha, Kužma, Jackuliak, Nachtmann, Max et al., Serum 25-hydroxyvitamin D Concentration Significantly Decreases in Patients with COVID-19 Pneumonia during the First 48 Hours after Hospital Admission, Nutrients,
doi:10.3390/nu14122362Soliman, Abdelaziz, Fathy, 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,
doi:10.1177/20101058211041405Sterne, Sutton, Ioannidis, Terrin, Jones et al., Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials, BMJ,
doi:10.1136/bmj.d4002Subramanian, Griffin, Hewison, Hopkin, Kenny et al., Vitamin D and COVID-19-Revisited, J Intern Med,
doi:10.1111/joim.13536Veroniki, Jackson, Viechtbauer, Bender, Bowden et al., Methods to estimate the between-study variance and its uncertainty in meta-analysis, Res Synth Methods,
doi:10.1002/jrsm.1164Villasis-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, Arch Med Res,
doi:10.1016/j.arcmed.2022.04.003Zhang, Xu, Ni, Small studies may overestimate the effect sizes in critical care metaanalyses: a meta-epidemiological study, Crit Care,
doi:10.1186/cc11919DOI record:
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"abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Randomised trials conducted before 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, these health benefits were not confirmed by larger randomised trials published after 2021.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To examine the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and on VDS for the prevention of ARI.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al., 2021. The associations between VDS vs no VDS, and admission to ICU were evaluated using random effect models. Meta-analyses were done for all trials and by groups trial size. Publication bias was assessed using the LFK index (no bias if index between -1 and +1) and the Trim and Fill method.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Nine trials on VDS for preventing admission to ICU were identified. The summary odds ratio (SOR) was 0.61 (95%CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (effect modification: p=0.04). The LFK index was -3.79, and after Trim and Fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (effect modification p=0.0001). The LFK index was -3.11, and after Trim and Fill, the SOR was 0.96 (0.88-1.05).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Strong publication bias affected randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.</jats:p></jats:sec>",
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