Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial

Abstract

Background: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection.

Methods: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software.

Results: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients.

Conclusions: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.

Keywords: COVID-19; Coronavirus; Interleukin 6; SARS-CoV-2; Tocilizumab.

Fig. 1

The study timeline.

Fig. 2

The cumulative incidence of death from baseline to day 28.

Fig. 3

The cumulative incidence of death from baseline to day 28 stratified according to clinical condition. Survival rate of severe group was 100% for 17 days, and reduced to 93.8% at day18 and maintained at this level until the end of study (day 24). In contrary, the survival rates of the critical group on day 17 was slightly more than 90.0% and dropped to 85.3%, 78.2% and 46.9% for 20, 22 and 24 days after starting tocilizumab therapy, respectively. Fall in lines shows the death event and small vertical lines show the improvement event. These censored cases (improvement event) are listed below: [In the severe group]: Days 4 (1 case), 7 (1 case), 10 (1 case), 15 (1 case), 20 (2 cases), 21 (2 cases), 23 (5 cases) and 24 (6 cases). [In the critical group]: Days 5 (1 case), 19 (2 cases), 20 (2 cases), 21 (2 case), 22 (3 cases), 23 (3 cases) and 24 (3 cases). Severe, patients with SpO2 < 90, RR > 30 or bilateral progressive lung infiltration; critical, patients who need ICU admission or need for mechanical ventilation; severe-censored, patients in the severe group who had dropped out the study; critical-censored, patients in the critical group who had dropped out the study.

Fig. 4

Initial non-contrast enhanced CT scan (A, B, and C) of a 26-year-old man with respiratory distress and positive PCR for SARS-CoV-2 showed bilateral multilobar ground glass opacities and consolidations with air-bronchogram with no pleural effusion (*), subsequent CT scan (D, E, and F) after injection of tocilizumab, revealed significant improvement with near complete resolution of parenchymal infiltration just with few remaining parenchymal infiltrations (arrows). CT, computed tomography.

Fig. 5

Portable CXR of 42-year-old man who was admitted to the intensive care unit after developing respiratory distress secondary to COVID induced pneumonia; initial CXR revealed bilateral confluent consolidations (*) after tocilizumab therapy, significant improvement of previous parenchymal consolidations was found with few remaining faintly visualized parenchymal infiltrations (arrows). (A, initial CXR, B, CXR after injection of tocilizumab). CXR, chest X-ray.