Abstract
Background: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment.
Methods: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW).
Results: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia.
Conclusions: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.
Keywords: COVID-19; SARS-CoV-2; interleukin-6; tocilizumab.
【저자키워드】 COVID-19, SARS-CoV-2, Tocilizumab, interleukin-6, 【초록키워드】 Treatment, coronavirus disease, Respiratory failure, mechanical ventilation, Tocilizumab, Pneumonia, inflammatory markers, intubation, outcome, Cytokine release syndrome, Probability, Cohort, survival, Characteristics, Patient, Effectiveness, Control, death, Follow-up, COVID-19 patients, Bacterial, primary endpoint, Staphylococcus aureus, Illness severity, IL-6 blockade, 95% CI, no difference, Fatality rate, chronic pulmonary disease, single-center, lower mortality, mechanically ventilated, multivariable Cox regression, D-dimer value, Weighting, Occurrence, proportion, evaluated, approved, elevated, accounted, less, groups, reduction in, cohort of patient, secondary analysis, with COVID-19,