Combination therapy of Tocilizumab and steroid for management of COVID-19 associated cytokine release syndrome

Abstract

Cytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednislone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroid in COVID-19 associated CRS.This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, India between April 2 and November 2, 2020. All patients administered TCZ and steroids during this period were included. The primary endpoint was incidence of all cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of systemic and infectious complications. Baseline and time dependent risk factors significantly associated with death were identified by Relative risk estimation.Out of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. Thirty seven percent patients were managed in wards and did not need intensive care unit (ICU) admission. Infectious complications like hospital acquired pneumonia, blood stream bacterial and fungal infections were observed in 2.13%, 2.13% and 0.06% patients respectively. Age ≥ 60 years (P = .014), presence of co-morbidities like hypertension (P = .011), IL-6 ≥ 100 pg/ml (P = .002), D-dimer ≥ 1000 ng/ml (P < .0001), CT severity index ≥ 18 (P < .0001) and systemic complications like lung fibrosis (P = .019), cardiac arrhythmia (P < .0001), hypotension (P < .0001) and encephalopathy (P < .0001) were associated with increased risk of death.Combination therapy of TCZ and steroids is likely to be safe and effective in management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled trials.

COVID-19-associated neurological sequelae: A case series on cerebral microbleeds and encephalopathy

“… 10 Despite the lack of consensus on treating COVID-19 patients; the commonly used medication is interleukin-6 (IL-6) receptor antagonist (tocilizumab). 22 In our case series, two (Cases I and II) out of the seven patients were treated with tocilizumab (TCZ), with one patient (Case II) having a favorable outcome. In a retrospective cohort study, 515 patients received TCZ and steroids, with an estimated 73.8% having clinical improvement.…”

Scars of COVID-19: A bibliometric analysis of post-COVID-19 fibrosis

“…Antifibrotic therapies against fibrosis due to COVID-19 were also reported. Antifibrotic agents involving pirfenidone and nintedanib ( 43 , 44 ), immune inhibitors ( 45 ), mesenchymal stem cell (MSC) therapy ( 46 , 47 ), lung transplantation ( 27 , 48 ), prolonged oxygen support, and rehabilitation exercise ( 49 ) might exert beneficial effects in preventing pulmonary fibrosis following COVID-19.…”

Prevention and treatment of ventilator-associated pneumonia in COVID-19

“…In contrast to this study, tocilizumab was reported to increase the incidence of VAP in critical COVID-19 patients ( Ceccarelli et al, 2021 ). In addition, it is reported that combination therapy of tocilizumab and steroids is likely to be conducive to managing COVID-19-associated cytokine release syndrome ( Dravid et al, 2021 ). While another research suggested that adding tocilizumab to methylprednisolone did not improve outcomes significantly ( Hamed et al, 2021 ).…”