ABSTRACT
Background. In November 2020, the FDA issued an Emergency Use Authorization (EUA) for casirivimab-imdevimab (CAS-IMD) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in certain high-risk patients. CAS-IMD is a monoclonal antibody cocktail that binds to COVID-19 spike protein receptor. Delta was the predominant strain in the US at the time. The purpose of this study is to evaluate if CAS-IMD administration to COVID-19 patients in the emergency department (ED) resulted in fewer hospitalizations and re-admissions. Methods. A retrospective chart review was conducted at Cleveland Clinic Martin Health which is composed of 3 hospitals and 1 free-standing ED. Patients with COVID-19 who met criteria for CAS-IMD in the ED from June 2021 to December 2021 were randomized into those who received CAS-IMD and those who did not. Patients were excluded if they had COVID-19 symptoms for >10 days or met EUA exclusion criteria for CAS-IMD. Cases and controls were matched by propensity score which was calculated by a logistic regression model including age, body mass index (BMI), sex, race and comorbidities. The primary outcome was the percentage of patients discharged from the ED who were hospitalized for COVID-19-related symptoms within 30 days. Secondary outcomes included number of CAS-IMD infusion-related reactions, ED return rate and subset analyses of severity of illness in the hospitalized. Statistical analyses were performed using two-sample t test or Wilcoxon rank sum test for continuous variables based on distribution, and Chi-square test or Fisher's exact test for categorical variables. Conditional logistic regression was used to compare the odds of hospitalization between groups. Results. Patients (N = 176) were matched 1:1 in each group. Eleven (12.5%) of the case group were hospitalized within 30 days of ED discharge vs. 36 (40.9%) in the control group. The odds of hospitalization in the CAS-IMD group were 81% lower than the control group (OR 0.19, 95% CI: 0.081-0.46, p< 0.001). After adjustment of covariates, the adjusted odds ratio remained significant (OR 0.12, 95% CI: 0.025-0.57, p=0.008). Conclusion. CAS-IMD use for mild-to-moderate COVID-19 infection in ED patients was associated with a lower incidence of hospitalization.
ABSTRACT
Background. Severe coronavirus disease 2019 (COVID-19) is associated with respiratory failure as well as thromboembolic and cardiovascular complications from dysregulated immune responses. Baricitinib (BAR), a Janus kinase (JAK) inhibitor, and tocilizumab (TZB), a monoclonal anti-interleukin-6 (IL-6) receptor antibody, earned Emergency Use Authorizations (EUA) from the Food and Drug Administration (FDA) for the treatment of COVID-19. This study aims to compare the effects of BAR and TZB in severe COVID-19. Methods. A retrospective chart review of patients admitted to Cleveland Clinic Martin Health with COVID-19 having received TZB or BAR was completed between 07/01/20 to 12/31/21. Exclusion criteria included patients who had received both agents in the same admission, received fewer than 5 doses of remdesivir, or were pregnant. The primary objective was to evaluate in-hospitalmortality. For secondary outcomes, hospital length of stay (LOS), intensive care unitLOS, readmission due to respiratory-related causes, progression to mechanical ventilation (MV) and CRP levels upon discharge or death were assessed. Safety outcomes were described by incidences of superimposed bacterial infections, thrombosis, and herpes simplex virus reactivation. Results. After adjustment of sex and CRP level, the odds of death in TZB was 86% higher than that of BAR group (OR 1.86, 95%CI 1.17-2.96, p=0.009). TZB group had more females (45% vs. 34%, p=0.036) and longer LOS (median [IQR]: 15 [10,23] vs. 13 [9,20], p=0.0390). TZB group had more organ support (47% vs. 29%, p< 0.001), more ICU admission and longer ICU LOS, moreMVprogression and longer duration of MV (36% vs. 22%, p=0.007;0[0,9] vs. 0[0,2], p< 0.001). TZB had more additional source of infection (25% vs. 16%, p=0.043) and more positive microbiology from blood (10% vs. 3%, p=0.009). Conclusion. Our findings suggest that BAR may have lower rates of in-hospital mortality when compared to TZB. TZB was also found to have higher needs for organ support. Superimposed infections, thrombosis, and HSV reactivation were similar in both groups. Larger randomized studies comparing these agents are needed.