Food Science; Nutrition and Dietetics; Vitamin D; COVID-19
Abstract :
[en] Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.
Disciplines :
Anesthesia & intensive care
Author, co-author :
De Niet, Sophie
Trémège, Mickaël
Coffiner, Monte
Rousseau, Anne-Françoise ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
CALMES, Doriane ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Frix, Anne-Noëlle ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
GESTER, Fanny ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Delvaux, Muriel ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
DIVE, Anne-Françoise ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
GUGLIELMI, Elora ; Centre Hospitalier Universitaire de Liège - CHU > > Unité équipe mobile Sart Tilman
Henket, Monique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Staderoli, Alicia ; Centre Hospitalier Universitaire de Liège - CHU > > Unité de chirurgie A NDB
Maesen, Didier ; Centre Hospitalier Universitaire de Liège - CHU > > Service officine et gaz médicaux
Louis, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Guiot, Julien ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Cavalier, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Holick M.F. Vitamin D deficiency N. Engl. J. Med. 2007 357 266 281 10.1056/NEJMra070553 17634462
Beard J.A. Bearden A. Striker R. Vitamin D and the anti-viral state J. Clin. Virol. 2011 50 194 200 10.1016/j.jcv.2010.12.006
Greiller C.L. Martineau A.R. Modulation of the immune response to respiratory viruses by vitamin D Nutrients 2015 7 4240 4270 10.3390/nu7064240 26035247
Coussens A.K. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease Photochem. Photobiol. Sci. 2017 16 314 338 10.1039/c6pp00355a
Lang P.O. Aspinall R. Vitamin D Status and the Host Resistance to Infections: What It Is Currently (Not) Understood Clin. Ther. 2017 39 930 945 10.1016/j.clinthera.2017.04.004 28457494
Gruber-Bzura B.M. Vitamin D and Influenza-Prevention or Therapy? Int. J. Mol. Sci. 2018 19 2419 10.3390/ijms19082419
Rondanelli M. Miccono A. Lamburghini S. Avanzato I. Riva A. Allegrini P. Faliva M.A. Peroni G. Nichetti M. Perna S. Self-Care for Common Colds: The Pivotal Role of Vitamin D, Vitamin C, Zinc, and Echinacea in Three Main Immune Interactive Clusters (Physical Barriers, Innate and Adaptive Immunity) Involved during an Episode of Common Colds-Practical Advice on Dosages and on the Time to Take These Nutrients/Botanicals in order to Prevent or Treat Common Colds Evid.-Based Complement. Altern. Med. ECAM 2018 2018 5813095 10.1155/2018/5813095
Gombart A.F. Pierre A. Maggini S. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection Nutrients 2020 12 236 10.3390/nu12010236
Jolliffe D.A. Camargo Jr C.A. Sluyter J.D. Aglipay M. Aloia J.F. Ganmaa D. Bergman P. Bischoff-Ferrari H.A. Borzutzky A. Damsgaard C.T. 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. 2021 9 276 292 10.1016/S2213-8587(21)00051-6
Hewison M. Vitamin D and immune function: An overview Proc. Nutr. Soc. 2012 71 50 61 10.1017/S0029665111001650
Wei R. Christakos S. Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D Nutrients 2015 7 8251 8260 10.3390/nu7105392 26404359
Fabbri A. Infante M. Ricordi C. Editorial—Vitamin D status: A key modulator of innate immunity and natural defense from acute viral respiratory infections Eur. Rev. Med. Pharmacol. Sci. 2020 24 4048 4052 10.26355/eurrev_202004_20876 32329882
Teymoori-Rad M. Marashi S.M. Vitamin D and COVID-19: From potential therapeutic effects to unanswered questions Rev. Med. Virol. 2021 31 e2159 10.1002/rmv.2159
Dijkman R. Jebbink M.F. Deijs M. Milewska A. Pyrc K. Buelow E. van der Bijl A. van der Hoek L. Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63 J. Gen. Virol. 2012 93 1924 1929 10.1099/vir.0.043919-0
Jolliffe D.A. Griffiths C.J. Martineau A.R. Vitamin D in the prevention of acute respiratory infection: Systematic review of clinical studies J. Steroid Biochem. Mol. Biol. 2013 136 321 329 10.1016/j.jsbmb.2012.11.017
Hansdottir S. Monick M.M. Hinde S.L. Lovan N. Look D.C. Hunninghake G.W. Respiratory epithelial cells convert inactive vitamin D to its active form: Potential effects on host defense J. Immunol. Baltim. Md. 1950 2008 181 7090 7099 10.4049/jimmunol.181.10.7090
Olliver M. Spelmink L. Hiew J. Meyer-Hoffert U. Henriques-Normark B. Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae J. Infect Dis. 2013 208 1474 1481 10.1093/infdis/jit355
Golpour A. Bereswill S. Heimesaat M.M. Antimicrobial and Immune-Modulatory Effects of Vitamin D Provide Promising Antibiotics-Independent Approaches to Tackle Bacterial Infections—Lessons Learnt from a Literature Survey Eur. J. Microbiol. Immunol. 2019 9 80 87 10.1556/1886.2019.00014
Moromizato T. Litonjua A.A. Braun A.B. Gibbons F.K. Giovannucci E. Christopher K.B. Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill Crit. Care Med. 2014 42 97 107 10.1097/CCM.0b013e31829eb7af 23982028
Thickett D.R. Moromizato T. Litonjua A.A. Amrein K. Quraishi S.A. Lee-Sarwar K.A. Mogensen K.M. Purtle S.W. Gibbons F.K. Camargo C.A. et al. Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: A retrospective cohort study BMJ Open Respir. Res. 2015 2 e000074 10.1136/bmjresp-2014-000074
Higgins D.M. Wischmeyer P.E. Queensland K.M. Sillau S.H. Sufit A.J. Heyland D.K. Relationship of vitamin D deficiency to clinical outcomes in critically ill patients JPEN J. Parenter. Enter. Nutr. 2012 36 713 720 10.1177/0148607112444449
Nair P. Lee P. Reynolds C. Nguyen N.D. Myburgh J. Eisman J.A. Center J.R. Significant perturbation of vitamin D-parathyroid-calcium axis and adverse clinical outcomes in critically ill patients Intensive Care Med. 2013 39 267 274 10.1007/s00134-012-2713-y 23064465
Braun A.B. Gibbons F.K. Litonjua A.A. Giovannucci E. Christopher K.B. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality Crit. Care Med. 2012 40 63 72 10.1097/CCM.0b013e31822d74f3
Quraishi S.A. Litonjua A.A. Moromizato T. Gibbons F.K. Camargo C.A. Jr. Giovannucci E. Christopher K.B. Association between prehospital vitamin D status and hospital-acquired Clostridium difficile infections JPEN J. Parenter. Enter. Nutr. 2015 39 47 55 10.1177/0148607113511991 24492311
Barnett N. Zhao Z. Koyama T. Janz D.R. Wang C.Y. May A.K. Bernard G.R. Ware L.B. Vitamin D deficiency and risk of acute lung injury in severe sepsis and severe trauma: A case-control study Ann. Intensive Care 2014 4 5 10.1186/2110-5820-4-5
Amrein K. Schnedl C. Holl A. Riedl R. Christopher K.B. Pachler C. Purkart T.U. Waltensdorfer A. Münch A. Warnkross H. et al. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: The VITdAL-ICU randomized clinical trial JAMA 2014 312 1520 1530 10.1001/jama.2014.13204 25268295
McNally J.D. Menon K. Chakraborty P. Fisher L. Williams K.A. Al-Dirbashi O.Y. Doherty D.R. The association of vitamin D status with pediatric critical illness Pediatrics 2012 130 429 436 10.1542/peds.2011-3059
Kempker J.A. West K.G. Kempker R.R. Siwamogsatham O. Alvarez J.A. Tangpricha V. Ziegler T.R. Martin G.S. Vitamin D status and the risk for hospital-acquired infections in critically ill adults: A prospective cohort study PLoS ONE 2015 10 e0122136 10.1371/journal.pone.0122136
Kaufman H.W. Niles J.K. Kroll M.H. Bi C. Holick M.F. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels PLoS ONE 2020 15 e0239252 10.1371/journal.pone.0239252
Angelidi A.M. Belanger M.J. Lorinsky M.K. Karamanis D. Chamorro-Pareja N. Ognibene J. Palaiodimos L. Mantzoros C.S. Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients Mayo Clin. Proc. 2021 96 875 886 10.1016/j.mayocp.2021.01.001
Meltzer D.O. Best T.J. Zhang H. Vokes T. Arora V. Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results JAMA Netw. Open 2020 3 e2019722 10.1001/jamanetworkopen.2020.19722 32880651
Han J.E. Jones J.L. Tangpricha V. Brown M.A. Hao L. Hebbar G. Lee M.J. Liu S. Brown L.A.S. Ziegler T.R. et al. High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial J. Clin. Transl. Endocrinol. 2016 4 59 65 10.1016/j.jcte.2016.04.004
Castillo M.E. Costa L.M.E. Barrios J.M.V. Díaz J.F.A. Miranda J.L. Bouillon R. Gomez J.M.Q. 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. 2020 203 105751 10.1016/j.jsbmb.2020.105751 32871238
Grant W.B. Lahore H. McDonnell S.L. Baggerly C.A. French C.B. Aliano J.L. Bhattoa H.P. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Nutrients 2020 12 988 10.3390/nu12040988 32252338
Cavalier E. Faché W. Souberbielle J.C. A Randomised, Double-Blinded, Placebo-Controlled, Parallel Study of Vitamin D3 Supplementation with Different Schemes Based on Multiples of 25,000 IU Doses Int. J. Endocrinol. 2013 2013 327265 10.1155/2013/327265
Schleck M.L. Souberbielle J.C. Jandrain B. Da Silva S. De Niet S. Vanderbist F. Scheen A. Cavalier E. A Randomized, Double-Blind, Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency Nutrients 2015 7 5413 5422 10.3390/nu7075227 26151178
De Niet S. Coffiner M. Da Silva S. Jandrain B. Souberbielle J.C. Cavalier E. A Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D3 Supplementation Nutrients 2018 10 659 10.3390/nu10060659 29882841
WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research Lancet Infect Dis. 2020 20 e192 e197 10.1016/S1473-3099(20)30483-7
Diagnostic Testing for SARS-CoV-2 Available online: https://www.who.int/publications-detail-redirect/diagnostic-testing-for-sars-cov-2 (accessed on 30 May 2022)
Wise S.A. Camara J.E. Sempos C.T. Lukas P. Le Goff C. Peeters S. Burdette C.Q. Nalin F. Hahm G. Durazo-Arvizu R.A. et al. Vitamin D Standardization Program (VDSP) intralaboratory study for the assessment of 25-hydroxyvitamin D assay variability and bias J. Steroid Biochem. Mol. Biol. 2021 212 105917 10.1016/j.jsbmb.2021.105917
Cavalier E. Fraser C.G. Bhattoa H.P. Heijboer A.C. Makris K. Ulmer C.Z. Vesper H.W. Vasikaran S. Lukas P. Delanaye P. et al. Analytical Performance Specifications for 25-Hydroxyvitamin D Examinations Nutrients 2021 13 431 10.3390/nu13020431 33525653
Cavalier E. Lukas P. Bekaert A.C. Peeters S. Le Goff C. Yayo E. Delanaye P. Souberbielle J.C. Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients Clin. Chem. Lab. Med. 2016 54 1347 1355 10.1515/cclm-2015-0923
Cavalier E. Lukas P. Crine Y. Peeters S. Carlisi A. Le Goff C. Gadisseur R. Delanaye P. Souberbielle J.C. Evaluation of automated immunoassays for 25(OH)-vitamin D determination in different critical populations before and after standardization of the assays Clin. Chim. Acta Int. J. Clin. Chem. 2014 431 60 65 10.1016/j.cca.2014.01.026 24508999
Murai I.H. Fernandes A.L. Sales L.P. Pinto A.J. Goessler K.F. Duran C.S. Silva C.B. Franco A.S. Macedo M.B. Dalmolin H.H. 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 1060 10.1001/jama.2020.26848 33595634
Cannata-Andía J.B. Díaz-Sottolano A. Fernández P. Palomo-Antequera C. Herrero-Puente P. Mouzo R. Carrillo-López N. Panizo S. Ibañez G.H. Cusumano C.A. 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. 2022 20 83 10.1186/s12916-022-02290-8 35177066
Milani G.P. Simonetti G.D. Edefonti V. Lava S.A. Agostoni C. Curti M. Stettbacher A. Bianchetti M.G. Muggli F. Seasonal variability of the vitamin D effect on physical fitness in adolescents Sci. Rep. 2021 11 182 10.1038/s41598-020-80511-x
Dopico X.C. Evangelou M. Ferreira R.C. Guo H. Pekalski M.L. Smyth D.J. Cooper N. Burren O.S. Fulford A.J. Hennig B.J. et al. Widespread seasonal gene expression reveals annual differences in human immunity and physiology Nat. Commun. 2015 6 7000 10.1038/ncomms8000
