Tocilizumab for the treatment of severe coronavirus disease 2019

Abstract

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.

Keywords: COVID-19; IL-6; SARS-CoV-2; coronavirus; tocilizumab.

Figure 1

Individual patient's summary of ventilatory support status from first day of tocilizumab therapy through 14 days follow up. Each horizontal line represents a single patient's respiratory support category on the days shown at the top of the figure. The shading denotes type of ventilatory support on that day. The markers represent days of tocilizumab administration and the dose received

Figure 2

Selected serial inflammatory markers from first day of tocilizumab therapy through 14 days follow up. Study day 1 is the day of initiation of tocilizumab therapy. Serial observations on study days 1, 3, 5, 7, 10, and 14 are shown. The tables denote values corresponding to the time points. Panel A: oral temperature in degrees celsius. Panel B: CRP in mg/L. Panel C: peripheral white cell count in cells (×10⁹/L). Panel D: peripheral lymphocyte count in cells (×10⁹/L). The dataset for the shown timepoint is complete for all included patients. The Wilcoxon signed‐rank test P values are shown for the comparisons indicated by the corresponding lines. CRP, C‐reactive protein

Figure 3

Summary of ventilatory support status from first day of tocilizumab therapy thru 14 days follow up (n = 25). Study day 1 is the day of initiation of tocilizumab therapy. Each horizontal line represents ventilation support categorization of the study cohort on the corresponding study day. The numbers indicate the count of individuals within each category at that time point