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Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study

Internal Medicine Department, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
CIBER Fisiopatologia Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
Internal Medicine Department, Regional University Hospital of Málaga, Avenida de Carlos Haya, s/n, 29010 Málaga, Spain
Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA), Avenida de Carlos Haya, s/n, 29010 Málaga, Spain
Internal Medicine Department, Hospital Costa del Sol, Agencia Sanitaria Costa del Sol, 29603 Marbella, Málaga, Spain
Internal Medicine Department, Alto Guadalquivir Hospital, Andújar, 23740 Jaén, Spain
Internal Medicine Department, Hospital de Montilla, Agencia Sanitaria Alto Guadalquivir, 14550 Córdoba, Spain
Pneumology Department, Reina Sofia University Hopital. Avda, Menendez Pidal s/n, 14004 Córdoba, Spain
Department of Medicine, University of Málaga (UMA), Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), 29071 Málaga, Spain
MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 02139, USA
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Herestraat, ON 1/902, 3000 Leuven, Belgium
IMIBIC. CIBER de Fragilidad y Envejecimiento Saludable, Hospital Universitario Reina Sofía, Universidad de Córdoba, Fundación Progreso y Salud, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
Author to whom correspondence should be addressed.
Both authors contributed equally to the work as co-first authors.
Both authors contributed equally to the work as co-senior authors.
Academic Editor: Jean Bousquet
Nutrients 2021, 13(6), 1760;
Received: 21 April 2021 / Revised: 10 May 2021 / Accepted: 14 May 2021 / Published: 21 May 2021
(This article belongs to the Section Clinical Nutrition)
Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings. View Full-Text
Keywords: COVID-19; calcifediol; SARS-CoV-2; COVID-19 drug treatment; vitamin D COVID-19; calcifediol; SARS-CoV-2; COVID-19 drug treatment; vitamin D
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MDPI and ACS Style

Alcala-Diaz, J.F.; Limia-Perez, L.; Gomez-Huelgas, R.; Martin-Escalante, M.D.; Cortes-Rodriguez, B.; Zambrana-Garcia, J.L.; Entrenas-Castillo, M.; Perez-Caballero, A.I.; López-Carmona, M.D.; Garcia-Alegria, J.; Lozano Rodríguez-Mancheño, A.; Arenas-de Larriva, M.d.S.; Pérez-Belmonte, L.M.; Jungreis, I.; Bouillon, R.; Quesada-Gomez, J.M.; Lopez-Miranda, J. Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study. Nutrients 2021, 13, 1760.

AMA Style

Alcala-Diaz JF, Limia-Perez L, Gomez-Huelgas R, Martin-Escalante MD, Cortes-Rodriguez B, Zambrana-Garcia JL, Entrenas-Castillo M, Perez-Caballero AI, López-Carmona MD, Garcia-Alegria J, Lozano Rodríguez-Mancheño A, Arenas-de Larriva MdS, Pérez-Belmonte LM, Jungreis I, Bouillon R, Quesada-Gomez JM, Lopez-Miranda J. Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study. Nutrients. 2021; 13(6):1760.

Chicago/Turabian Style

Alcala-Diaz, Juan F., Laura Limia-Perez, Ricardo Gomez-Huelgas, Maria D. Martin-Escalante, Begoña Cortes-Rodriguez, Jose L. Zambrana-Garcia, Marta Entrenas-Castillo, Ana I. Perez-Caballero, Maria D. López-Carmona, Javier Garcia-Alegria, Aquiles Lozano Rodríguez-Mancheño, Maria del Sol Arenas-de Larriva, Luis M. Pérez-Belmonte, Irwin Jungreis, Roger Bouillon, Jose Manual Quesada-Gomez, and Jose Lopez-Miranda. 2021. "Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study" Nutrients 13, no. 6: 1760.

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