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.
【저자키워드】 COVID-19, intensive care, mechanical ventilation, Tocilizumab, Steroids, Cytokine release syndrome, Infectious complications, 【초록키워드】 Dexamethasone, Treatment, Cytokine storm, therapy, Randomized controlled trials, Mortality, Anti-inflammatory, mechanical ventilation, Tocilizumab, Pneumonia, IL-6, severity, hospital, India, Ventilation, intensive care unit, interleukin-6, fibrosis, D-dimer, combination therapy, outcome, risk factor, hypertension, Steroids, Relative risk, ICU, Cardiac arrhythmia, Cytokine release syndrome, management, Hypotension, Patient, Infectious complications, death, co-morbidity, Complication, Clinical improvement, Encephalopathy, Efficacy and safety, Lung fibrosis, incidence, Admission, patients, co-morbidities, interleukin-6 receptor, Bacterial, CRS, primary endpoint, Fungal infection, Safe, steroid, lung damage, receptor antagonist, not need, retrospective cohort study, ventilator, increased risk, Secondary outcomes, worsening, morbidities, inflammatory lung damage, syndrome, bacterial and fungal infections, blood stream, Administered, Hospital acquired, females, effective, secondary, Seven, thought, evaluate, significantly, required, approved, conducted, Mechanical, patients with COVID-19, TCZ, 【제목키워드】 therapy, Tocilizumab, management, single center,