ALBACOVIDIOL Study: Effect of Calcifediol Treatment on Mortality in Patients Hospitalized for COVID-19: A Retrospective Analysis
José Antonio Blázquez-Cabrera, Javier Torres-Hernández, Roger Bouillon, Antonio Casado-Díaz, José Manuel Quesada-Gomez, Laura Navarro-Casado
Nutrients, doi:10.3390/nu17121968
Background: Immunomodulatory treatments targeting excessive host immune responses favorably shifting the course of COVID-19. High doses of calcifediol may reduce the mortality of this infection. Objective: To evaluate how a high dose of calcifediol modifies the risk of death in patients hospitalized with COVID-19 during the first outbreaks. Design: A retrospective, observational study to evaluate the relationship between treatment with calcifediol and the risk of death in patients hospitalized with COVID-19 at the "Complejo Hospitalario Universitario de Albacete" (CHUA), Spain, during the months of January to March 2021. Patients were treated with corticosteroids, and some patients also received baricitinib and/or high doses of calcifediol, according to CHUA's therapeutic protocol 2021 for COVID-19. The primary outcome measure was mortality according to calcifediol treatment. Results: A total of 230 patients were included. 25(OH)D levels were measured on admission in 148 patients, showing a high prevalence of vitamin D deficiency [median 25(OH)D: 17.5 ng/mL]. Thirty-four (23%) had severe deficiency (25(OH)D ≤ 10 ng/mL). In the 119 patients (51.7%) who received in-hospital treatment with a high dose of calcifediol, the mortality rate was 12.6% (15 cases, 95% confidence interval [CI], 7.8-19.8%), while in 111 patients who did not receive treatment with calcifediol, the death rate was 23.4% (26 cases, 95% CI: 16.5-32.1%; p = 0.039). The odds ratio (OR) in treated vs. untreated patients was 0.47 (95% CI: 0.23-0.95). Among the patients admitted with severe deficiency, 16 received treatment with calcifediol, with a mortality rate of 0.0% (0 cases, 95% CI: 0.0-19.4%), while in the 18 not treated with calcifediol, a death rate of 38.9% was observed (7 cases, 95% CI: 20.3-61.4%; p = 0.008). The mortality rate was lower in patients treated with the combination of calcifediol and corticosteroids vs. those treated with corticosteroids alone (p = 0.038) and vs. those treated with corticosteroids and baricitinib (p = 0.033). Conclusions: In the ALBACOVIDIOL study, calcifediol treatment was associated with a lower observed mortality rate in hospitalized patients with COVID-19 treated with corticosteroids (with or without baricitinib), especially in those with severe vitamin D deficiency. Causality cannot be inferred due to the retrospective study design.
Informed Consent Statement: The Biomedical Research Ethics Committee of the Complejo Hospitalario Universitario de Albacete (CHUA), Spain approved the study for secondary use of clinical data for research purposes. The study did not require informed consent as the investigators handled completely anonymized data without any reference to personal data that could allow identification by any means. All research was conducted in accordance with the relevant guidelines and regulations.
Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
Appendix A
Collaborators in Data Collection Teresa Granero-Salas, Andrea Pérez-Trujillo, Marta Guzman-Pérez, Marcos-Alexander Ostaiza-Ordoñez, Rocio Garvi-Merino, Jordi Olucha-Puchol, Cristina Garcia-Gomez, Cristina del Pozo-Carlavilla, Belen Serna-Serrano, Juan Manuel Collado-Sanz, Hector Alabort-Ayllón, Beira da Silva-Cabañero.
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