Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: a retrospective cohort study with follow-up from Mumbai, India

Abstract

Background Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. Method This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. Results Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427–0.903, P 0.013) and higher oxygen saturation. Conclusion Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Tocilizumab treatment for COVID-19 patients: a systematic review and meta-analysis

“…Overall, 10 201 patients from 25 different publications were included in this study. Seven of the studies assessed patients from the USA [ 10 , 15 – 20 ], 13 of the studies assessed patients from west Europe [ 8 , 21 – 32 ], two assessed patients from multiple countries [ 33 , 34 ], one assessed patients from Brazil [ 35 ], and two studies were from India [ 36 , 37 ]. The main characteristics of the 25 included studies were summarized in Table 1 .…”

Single versus multiple doses of Tocilizumab in critically ill patients with coronavirus disease 2019 (COVID-19): A two-center, retrospective cohort study

“…Several RCTs and observational studies have evaluated either single or multiple doses of tocilizumab in patients with COVID-19. Yet, tocilizumab's safety and e cacy results compared to standard care or placebo are contradicting [12], [13], [15], [17], [18], [23], [24].…”

Common points of therapeutic intervention in COVID-19 and in allogeneic hematopoietic stem cell transplantation associated severe cytokine release syndrome

“…A total of 1805 patients receiving TCZ were enrolled in 18 retrospective studies on severe COVID-19 patients [45,47,48]. Mortality reduction was shown only in 9 studies [53][54][55][56][57][58][59][60][61]. A comprehensive overview of the pathophysiological role of IL-6 in autoimmune inflammatory processes and CRS and the results of anti-IL-6 in CAR-T cell treatment and COVID-19 infection is available by Kishimoto [31].…”