Matched cohort study on the efficacy of tocilizumab in patients with COVID-19.

BACKGROUND: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. METHODS: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. RESULTS: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: -0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). CONCLUSIONS: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge.

Association between COVID-19 prognosis and disease presentation, comorbidities and chronic treatment of hospitalized patients.

IMPORTANCE: The rapid pandemic expansion of the disease caused by the new SARS-CoV-2 virus has compromised health systems worldwide. Knowledge of prognostic factors in affected patients can help optimize care. OBJECTIVE: The objective of this study was to analyze the relationship between the prognosis of COVID-19 and the form of presentation of the disease, the previous pathologies of patients and their chronic treatments. DESIGN, PARTICIPANTS AND LOCATIONS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia (Spain). As primary outcomes, severe disease (need for oxygen therapy via nonrebreather mask or mechanical ventilation) and death were studied. Multivariate binary logistic regression models were performed to study the association between the different factors and the results. RESULTS: Advanced age, male sex and obesity were independent markers of poor prognosis. The most frequent presenting symptom was fever, while dyspnea was associated with severe disease and the presence of cough with greater survival. Low oxygen saturation in the emergency room, elevated CRP in the emergency room and initial radiological involvement were all related to worse prognosis. The presence of eosinophilia (% of eosinophils) was an independent marker of less severe disease. CONCLUSIONS: This study identified the most robust markers of poor prognosis for COVID-19. These results can help to correctly stratify patients at the beginning of hospitalization based on the risk of developing severe disease.

Observational study of azithromycin in hospitalized patients with COVID-19.

BACKGROUND: The rapid spread of the disease caused by the novel SARS-CoV-2 virus has led to the use of multiple therapeutic agents whose efficacy has not been previously demonstrated. The objective of this study was to analyze whether there is an association between the use of azithromycin and the evolution of the pulmonary disease or the time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI ratio (oxygen saturation/fraction of inspired oxygen) in the first 48 hours of treatment and the time to discharge. The results were compared between patients treated and untreated with the study drug through subcohort analyses matched for multiple clinical and prognostic factors, as well as through analysis of non-matched subcohorts, using Cox multivariate models adjusted for prognostic factors. RESULTS: There were 239 patients treated with azithromycin. Of these, 29 patients treated with azithromycin could be matched with an equivalent number of control patients. In the analysis of these matched subcohorts, SAFI at 48h had no significant changes associated to the use of azithromycin, though azithromycin treatment was associated with a longer time to discharge (10.0 days vs 6.7 days; log rank: p = 0.039). However, in the unmatched cohorts, the increased hospital stay associated to azithromycin use, was no significant after adjustment using Multivariate Cox regression models: hazard ratio 1.45 (IC95%: 0.88-2.41; p = 0.150). This study is limited by its small sample size and its observational nature; despite the strong pairing of the matched subcohorts and the adjustment of the Cox regression for multiple factors, the results may be affected by residual confusion. CONCLUSIONS: We did not find a clinical benefit associated with the use of azithromycin, in terms of lung function 48 hours after treatment or length of hospital stay.