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

被引:502
作者
Entrenas Castillo, Marta [1 ]
Entrenas Costa, Luis Manuel [1 ]
Vaquero Barrios, Jose Manuel [1 ]
Alcala Diaz, Juan Francisco [2 ]
Lopez Miranda, Jose [2 ]
Bouillon, Roger [3 ]
Quesada Gomez, Jose Manuel [4 ]
机构
[1] Univ Cordoba, Inst Maimonides Invest Biomed Cordoba IMIBIC 9, UGC Neumol, Hosp Univ Reina Sofia, Avda Menendez 10 Pidal S-N, Cordoba 1400411, Spain
[2] Univ Cordoba, CIBER Fisiopatol Obesidad & Nutr, Dept Med Interna, Hosp Univ Reina Sofia,IMIBIC,Fdn Progreso & Salud, Avda Menendez Pidal S-N, Cordoba 1400414, Spain
[3] Katholieke Univ Leuven, Lab Clin & Expt Endocrinol, Dept Chron Dis Metab & Ageing, Herestr ON1-902, B-3000 Leuven, Belgium
[4] Univ Cordoba, Hosp Univ Reina Sofia, Fdn Progreso & Salud, IMIBIC,CIBER Fragilidad & Envejecimiento Saludabl, Avda Menendez Pidal S-N, Cordoba 1814004, Spain
关键词
COVID-19; SARS-CoV-2; Vitamin D; Vitamin D3 or cholecalciferol; Calcifediol or 25-hydroxyvitamin D3; 1; alpha; 25(OH)2D or 1 alpha; 25-dihydroxyvitamin D or calcitriol; Acute respiratory distress syndrome (ARDS); Cytokine/Chemokine storm; Renin-angiotensin system; Hypercoagulability; Hydroxychloroquine; Chloroquine; Covidiol; Neutrophil activity; Vitamin D endocrine system; Cuboidal alveolar coating cells type II; Cathelicidin peptide; Defensins; TLR co-receptor CD14; Vitamin D receptor; RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; VITAMIN-D; GUIDELINES;
D O I
10.1016/j.jsbmb.2020.105751
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Objective: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly in- crease serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. Design: Parallel pilot randomized open label, double-masked clinical trial. Setting: University hospital setting (Reina Sofia University Hospital, Cordoba Spain.) Participants: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). Procedures: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. Results: Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X-2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. Conclusion: Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
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相关论文
共 41 条
[1]   Both 25-Hydroxyvitamin-D3 and 1,25-Dihydroxyvitamin-D3 Reduces Inflammatory Response in Human Periodontal Ligament Cells [J].
Andrukhov, Oleh ;
Andrukhova, Olena ;
Hulan, Ulamnemekh ;
Tang, Yan ;
Bantleon, Hans-Peter ;
Rausch-Fan, Xiaohui .
PLOS ONE, 2014, 9 (02)
[2]  
[Anonymous], 2020, NATURE, DOI DOI 10.1038/s41586-020-2012-7
[3]  
[Anonymous], 2020, The lancet
[4]   Randomized Clinical Trials and COVID-19 Managing Expectations [J].
Bauchner, Howard ;
Fontanarosa, Phil B. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (22) :2262-2263
[5]   Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries [J].
Bellani, Giacomo ;
Laffey, John G. ;
Pham, Tai ;
Fan, Eddy ;
Brochard, Laurent ;
Esteban, Andres ;
Gattinoni, Luciano ;
van Haren, Frank ;
Larsson, Anders ;
McAuley, Daniel F. ;
Ranieri, Marco ;
Rubenfeld, Gordon ;
Thompson, B. Taylor ;
Wrigge, Hermann ;
Slutsky, Arthur S. ;
Pesenti, Antonio .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2016, 315 (08) :788-800
[6]   Vitamin D Metabolism Revised: Fall of Dogmas [J].
Bouillon, Roger ;
Bikle, Dan .
JOURNAL OF BONE AND MINERAL RESEARCH, 2019, 34 (11) :1985-1992
[7]   Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions [J].
Bouillon, Roger ;
Marcocci, Claudio ;
Carmeliet, Geert ;
Bikle, Daniel ;
White, John H. ;
Dawson-Hughes, Bess ;
Lips, Paul ;
Munns, Craig F. ;
Lazaretti-Castro, Marise ;
Giustina, Andrea ;
Bilezikian, John .
ENDOCRINE REVIEWS, 2019, 40 (04) :1109-1151
[8]   25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2 [J].
D'Avolio, Antonio ;
Avataneo, Valeria ;
Manca, Alessandra ;
Cusato, Jessica ;
De Nicolo, Amedeo ;
Lucchini, Renzo ;
Keller, Franco ;
Cantu, Marco .
NUTRIENTS, 2020, 12 (05)
[9]   Acute Respiratory Distress Syndrome Advances in Diagnosis and Treatment [J].
Fan, Eddy ;
Brodie, Daniel ;
Slutsky, Arthur S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2018, 319 (07) :698-710
[10]   Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 [J].
Geleris, Joshua ;
Sun, Yifei ;
Platt, Jonathan ;
Zucker, Jason ;
Baldwin, Matthew ;
Hripcsak, George ;
Labella, Angelena ;
Manson, Daniel K. ;
Kubin, Christine ;
Barr, R. Graham ;
Sobieszczyk, Magdalena E. ;
Schluger, Neil W. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (25) :2411-2418