Response to Tocilizumab in Severe COVID 19

Background: Since the COVID-19 pandemic began in December 2019 no specific therapy for managing severe complications of infection has emerged, although this is under intensive investigation. Progressive pneumonia and multi-organ complications are managed with supportive care and COVID-19 has a mortality of >50% when ventilatory support is needed.Methods: We implemented a compassionate use protocol for tocilizumab, a humanised monoclonal anti-Il-6 receptor antibody. Patients with severe COVID-19 requiring oxygen or ventilation, and complicated by hyperinflammation and the cytokine release syndrome (CRS) received tocilizumab (8 mg/kg up to a maximum of 800 mg, with the option of a second dose given after 12-24 hours). CRS was defined as having at least three of: D-dimer above the upper limit of normal (ULN), rising C-reactive protein (CRP), ferritin >1000 ng/mL and lactate dehydrogenase (LDH) greater than the ULN.Oral consent for prescription of an off-label medicine was obtained from patients, their next of kin or representative, whenever possible. The treatment protocol adhered to the Monitored Emergency Use of Unregistered and Investigational Interventions of the WHO.Findings: Of seventeen patients with severe COVID-19 seen between 3-12th April 2020, eleven patients (seven ventilated and four receiving high flow oxygen) were treated with tocilizumab. Treatment normalised temperatures within 48 hours and was associated with a significant fall in CRP from 311 (138-332) (median, IQR mg/L) to 110 (58-184) (p = 0·001). For the group, oxygen requirements fell by 60±32% (95% CI 38-81) over 1 week (p<0·001). Two of seven patients on intensive care died, five have been extubated and two discharged. All four ward patients have also been discharged.Interpretation: Following tocilizumab treatment, we observed improvement in clinical and laboratory abnormalities in this small series. Compassionate use of tocilizumab can provide valuable information to support clinical trials in patients with severe COVID-19.