Tocilizumab Use in COVID-19 Cytokine-release Syndrome: Retrospective Study of Two Centers

Abstract

A bstract Introduction Cytokine-release syndrome (CRS) in COVID-19 patients can cause multiorgan failure and higher mortality. We used a structured protocol based on clinical, biochemical, and interleukin 6 (IL-6) criteria for the identification of the subset of patients with CRS and analyzed the use of tocilizumab for their treatment. Materials and methods We did a retrospective case-control analysis of all COVID-19 patients between 15 March and 15 May 2020 with severe to critical disease in ICU. They were evaluated for CRS, and 22 patients who met the criterion were given tocilizumab. The primary objective was to evaluate the effect of tocilizumab on escalation of respiratory support and ICU mortality. The secondary objectives were ICU length of stay, trends of inflammatory markers, and any adverse effects. Results The need for escalation of respiratory support was significantly lower in the tocilizumab group as compared to standard treatment ( p = 0.001). The mortality at day 7 and 28 was also significantly lower in the tocilizumab group ( p = 0.007 and p = 0.001 respectively). There was a significant reduction in C-reactive protein (CRP) who received tocilizumab ( p = 0.033). Conclusion In our limited number of patients, timely intervention with tocilizumab in COVID-19 patients with CRS significantly improved overall ICU outcome by reducing the need for invasive ventilation and mortality. How to cite this article Nasa P, Singh A, Upadhyay S, Bagadia S, Polumuru S, Shrivastava PK, et al. Tocilizumab Use in COVID-19 Cytokine-release Syndrome: Retrospective Study of Two Centers. Indian J Crit Care Med 2020;24(9):771–776.

When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It

“…The treatments proposed in various studies have included corticosteroid therapies (commonly used to suppress inflammation), Janus kinase (JAK) inhibitors (IL-1 family antagonists) or IL-6 receptor blockade (IL-6 antagonists), and TNF blockers. The randomized controlled COVACTA trial NCT04320615 (A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia)failed to meet its primary end point of improved clinical status [ 43 ], but evidence in the literature, instead, reports efficacy with tocilizumab [ 44 , 45 , 46 ]. Care should be taken in interpreting data from the COVACTA study, one consideration is that something must be done about the timing of the administration, because the immunosuppression (with glucocorticoids or IL-6 blockade) needs to intervene when the immune response makes the patient sick.…”

“…The COVACTA trial missed clinically relevant differences between patient groups [ 47 ]. In fact, in studies reporting efficacy of tocilizumab, the administration was related to the presence of hyperinflammatory syndrome [ 45 , 46 ]. The RECOVERY trial NCT04381936 (Randomised Evaluation of COVID-19 Therapy) results show a clear benefit of dexamethasone in patients who require respiratory support, but not in patients who do not require respiratory support.…”

Targeting COVID-19 Based on Pathogenesis

“…In severe to critical COVID-19 disease with hypercytokinemia in ICU, tocilizumab significantly reduced inflammatory response illustrated by the decrease in CRP, decreased the requirement of respiratory sup-port, and lowered the mortality (Nasa et al, 2020). The cases with unfavorable outcomes after tocilizumab treatment were linked to the failure in reducing the level of CRP (Luo, Liu, Qiu, Liu, Liu & Li, 2020).…”