Therapeutic outcomes following tocilizumab administration in patients with severe COVID-19

ABSTRACT

INTRODUCTION: Immunomodulation has been suggested as a treatment for COVID-19 to manage the hyperinflammatory state caused by cytokine release. Tocilizumab (TCZ) is an interleukin-6 (IL-6) monoclonal antibody approved for T-cell therapy induced cytokine release syndrome (CRS) and may provide benefit in COVID-19 patients with CRS. This study was conducted to assess clinical outcomes in patients with severe COVID-19 treated with TCZ. METHODS: Retrospective, single center, cohort study of adults with severe COVID-19 admitted to the intensive care unit who received TCZ between March 2020 to April 2020. All doses of TCZ were 400 mg given intravenously. A control group of severe COVID-19 patients who did not receive TCZ was randomly selected for comparison based upon similar baseline demographics (APACHE IV, SOFA score, age, gender, mechanical ventilation, multi-system organ failure (MSOF), and prone therapy). COVID-19 treatments received, temperature, inflammatory markers, mortality, diagnosis of superimposed infection and length of stay (LOS) was also collected. RESULTS: 25 patients who received TCZ and 17 patients who did not receive TCZ were included in the study. Baseline demographics were not significantly different between the TCZ vs. control group (APACHE IV = 53 vs. 55;SOFA score = 6.7 vs. 7.2). All patients were mechanically ventilated and 88% of patients in each group were diagnosed with MSOF. Maximum temperature and inflammatory markers were not significantly different (median IL-6 = 157.8 pg/mL vs. 131.5 pg/mL). There was no significant difference between the number of patients who received hydroxychloroquine, azithromycin, steroids, remdesivir, or convalescent plasma. 16 patients (64%) in the TCZ group received one dose and 9 (36%) received two doses. The mortality rate was not significantly different (8/25, 32% vs. 5/17, 29%;p = 0.86). The incidence of superimposed infection following TCZ administration was significantly higher compared to the incidence of superimposed infection at any time during admission for the control group (18/25, 72% vs. 7/17, 41%;p = 0.045). Mean LOS was 27 days vs. 19 days. CONCLUSIONS: There was no significant difference in mortality in COVID-19 patients who received TCZ. Our study suggests that patients who receive TCZ are at a significantly higher risk of infection.