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

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.

Efficacy and safety of early treatment with sarilumab in hospitalised adults with COVID-19 presenting cytokine release syndrome (SARICOR STUDY): protocol of a phase II, open-label, randomised, multicentre, controlled clinical trial.

INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.