Tocilizumab in patients with severe COVID-19: A single-center observational analysis

Abstract

Patients with coronavirus disease 2019 (COVID-19) may develop severe respiratory distress, thought to be mediated by cytokine release. Elevated proinflammatory markers have been associated with disease severity. Tocilizumab, an interleukin-6 receptor antagonist, may be beneficial for severe COVID-19, when cytokine storm is suspected. This is a retrospective single-center analysis of the records of patients diagnosed with COVID-19 who received tocilizumab. Outcomes, including clinical improvement, mortality and changes in oxygen-support at 24, 48, and 72 hours, and 7, 14, and 28 days post-tocilizumab, are reported. Patients were evaluated by baseline pre-tocilizumab oxygenation status and changes in proinflammatory markers within 7 days post-tocilizumab are reported. Sixty-six patients received tocilizumab at a mean dose of 724 mg (7.4 mg/kg), 3.7 days from admission. At baseline, 53% of patients were on ventilation support and all had elevated proinflammatory markers, including c-reactive protein (CRP). Common comorbidities were diabetes mellitus (43%) and hypertension (74%). Most patients received concomitant glucocorticoids and hydroxychloroquine. Seven days after tocilizumab, ten patients (15.2%) had clinical improvement in their oxygenation status, and there was a 95% decrease in CRP. Within 14 days of treatment, 29% of patients had clinical improvement, 20% had minimal or no improvement, 17% worsened, 27% died, and 7% were transferred to an outside hospital. Ultimately, 42% of all patients that received tocilizumab expired and 49% were discharged. This study found limited clinical improvement in patients that received tocilizumab in the setting of severe COVID-19. Clinical trials are ongoing to further evaluate tocilizumab's benefit in this patient population.

Keywords: COVID-19; IL-6 antagonist; cytokine release syndrome; cytokine storm; tocilizumab.

Figure 1

Kaplan‐Meier curves for (A) 28‐day survival and (B) 28‐day clinical improvement

Figure 2

Comparison of clinical status over time by baseline oxygenation status. Definitions: clinical improvement (decrease two or more points on the ordinal scale), improved oxygenation (decrease one point on the ordinal scale), worsened oxygenation (increase one or more points on the ordinal scale, excluding death)

Figure 3

Changes in inflammatory markers from baseline to 7 days post‐tocilizumab. Median, interquartile range, and range of inflammatory markers of patients that had evaluable levels at baseline and post‐tocilizumab day‐7. CRP, c‐reactive protein; LDH, lactate dehydrogenase

Figure 4

Comparison of baseline inflammatory markers by overall clinical outcome 14 days post‐tocilizumab. There were no clear associations with baseline inflammatory marker level and ultimate clinical outcome by post‐tocilizumab day‐14. CRP, c‐reactive protein; LDH, lactate dehydrogenase