1. 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
- Author
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Roger Bouillon, José López Miranda, Luis Manuel Entrenas Costa, Marta Entrenas Castillo, José Manuel Vaquero Barrios, José Manuel Quesada Gómez, Juan Francisco Alcalá Díaz, [Entrenas Castillo,M, Entrenas Costa,LM, Vaquero Barrios,JM] UGC de Neumología, Instituto Maimónides de Investigación Biomédica de Córdoba 9 (IMIBIC). Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain. [Alcalá Díaz,JF, and López Miranda,J] Departamento de Medicina Interna. IMIBIC, CIBER de Fisiopatología de la Obesidad y la Nutrición. Hospital Universitario Reina Sofía, Universidad de Córdoba, Fundación Progreso y Salud. Córdoba, Spain. [Bouillon] Department of Chronic Diseases, Metabolism and Ageing, Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. [Quesada Gomez,JM] IMIBIC. CIBER de Fragilidad y Envejecimiento Saludable. Hospital Universitario Reina Sofía, Universidad de Córdoba, Fundación Progreso y Salud. Córdoba, Spain.
- Subjects
0301 basic medicine ,Male ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,RESPIRATORY-DISTRESS-SYNDROME ,Pilot Projects ,CORONAVIRUS ,Azithromycin ,GUIDELINES ,Biochemistry ,law.invention ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Defensins ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,law ,Medicine ,Acute respiratory distress syndrome (ARDS) ,Vitamin D ,Cathelicidin peptide ,VITAMIN-D ,Bone Density Conservation Agents ,Mortality rate ,Respiratory infection ,Chloroquine ,Middle Aged ,Prognosis ,Calcifediol or 25-hydroxyvitamin D3 ,Covidiol ,Intensive care unit ,Hospitalization ,Cytokine/Chemokine storm ,Intensive Care Units ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization [Medical Subject Headings] ,030220 oncology & carcinogenesis ,1 alpha, 25(OH)2D or 1 alpha, 25-dihydroxyvitamin D or calcitriol ,Molecular Medicine ,Female ,Renin-angiotensin system ,Coronavirus Infections ,Life Sciences & Biomedicine ,medicine.drug ,Hydroxychloroquine ,medicine.medical_specialty ,Biochemistry & Molecular Biology ,Randomization ,1α, 25(OH)2D or 1α, 25-dihydroxyvitamin D or calcitriol ,Pneumonia, Viral ,Check Tags::Male [Medical Subject Headings] ,Diseases::Respiratory Tract Diseases::Respiratory Tract Infections::Pneumonia [Medical Subject Headings] ,Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Units::Intensive Care Units [Medical Subject Headings] ,TLR co-receptor CD14 ,Article ,03 medical and health sciences ,Betacoronavirus ,Endocrinology & Metabolism ,Hypercoagulability ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Bone Density Conservation Agents [Medical Subject Headings] ,Double-Blind Method ,Internal medicine ,Humans ,Molecular Biology ,Pandemics ,Calcifediol ,Vitamin D3 or calcitriol ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Pilot Projects [Medical Subject Headings] ,Science & Technology ,Chemicals and Drugs::Polycyclic Compounds::Steroids::Secosteroids::Vitamin D::Cholecalciferol::Hydroxycholecalciferols::Calcifediol [Medical Subject Headings] ,Vitamin D endocrine system ,business.industry ,SARS-CoV-2 ,Cuboidal alveolar coating cells type II ,Vitamin D3 or cholecalciferol ,Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings] ,COVID-19 ,Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,COMMUNITY-ACQUIRED PNEUMONIA ,Cell Biology ,Neutrophil activity ,Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings] ,Clinical trial ,030104 developmental biology ,Check Tags::Female [Medical Subject Headings] ,chemistry ,Vitamin D receptor ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Double-Blind Method [Medical Subject Headings] ,business - Abstract
Highlights • The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression. • Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19. • Calcifediol seems to be able to reduce severity of the disease., 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 increase 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, Córdoba 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 X2 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.
- Published
- 2020