Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study
Juan F Alcala-Diaz, 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, Jose Lopez-Miranda
Nutrients, doi:10.3390/nu13061760
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 D 3 ) 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 Nutrients 2021, 13, 1760. https://doi.org/10.3390/nu13061760 https://www.mdpi.com/journal/nutrients ≥ 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.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: JFAD received lecture fees from Bayer, Grunenthal Pharma, Esteve, Ferrer, and Boehringer Ingelheim outside the submitted work. LLP received lecture fees from Gebro Pharma S.A., Boehringer Ingelheim, Pfizer, Mylan, Almirall, SANOFI, and ESTEVE outside the submitted work. IJ, RGH, MDME, BCR, JLZG, MEC, AIPC, MDLC, JGA, ALRM, MDSAL, and LMPB have nothing to declare. RB received lecture fees from Abiogen, Faes Farma, Fresenius, and Proctor and Gamble outside the submitted work. JMQG received lecture fees from FAES Farma (Spain) and Amgen related to vitamin D-these activities in no way influenced the writing of the present manuscript. JLM received lecture fees from AMGEN, SANOFI, FERRER, Laboratorios Dr. Esteve, and Boehringer Ingelheim-Lilly outside the submitted work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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'abstract': '<jats:p>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.</jats:p>',
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