Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes.
【저자키워드】 Infectious diseases, Health care, 【초록키워드】 COVID-19, Cytokine storm, therapy, Tocilizumab, antibody, interleukin-6, Comorbidity, Gender, C-reactive protein, D-dimer, predictors, outcome, Cytokine release syndrome, outcomes, Nasopharyngeal swab, Patient, nasopharynx, death, SOFA, receptor, predictor, Responder, disease, patients, monoclonal, Signaling, Biological, Safe, criteria, clinical manifestation, SOFA score, In-hospital, Systolic blood pressure, profile, inclusion criteria, Stage, Final, blockade, key factor, severely ill patients, humanized, non-responder, Prevent, consequence, initial, catastrophic, plasma biomarker, predicted, collected, evaluated, treated, contributing to, implicated, Temporal, anticipated, clinical marker, patients hospitalized, the SARS-CoV-2, with COVID-19, 【제목키워드】 interleukin-6, blockade, patients with COVID-19,