Department of Infectious Diseases and HIV/AIDS, Noble hospital and Research Centre, Pune, Maharashtra, India.
Department of Medicine, Noble hospital and Research Centre, Pune, Maharashtra, India.
Medicine (Baltimore). 2021 Jul 23;100(29):e26705. doi: 10.1097/MD.0000000000026705.
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.
细胞因子释放综合征（CRS）或细胞因子风暴被认为是导致 COVID-19 患者肺部炎症损伤、肺炎恶化和死亡的原因。在印度，类固醇（甲泼尼龙或地塞米松）和托珠单抗（TCZ），一种白细胞介素-6 受体拮抗剂，被批准用于治疗 CRS。本研究旨在评估 TCZ 和类固醇联合治疗 COVID-19 相关 CRS 的疗效和安全性。
这项回顾性队列研究于 2020 年 4 月 2 日至 11 月 2 日在印度浦那的 Noble 医院和研究中心（NHRC）进行。在此期间接受 TCZ 和类固醇治疗的所有患者均被纳入研究。主要终点是全因死亡率。次要结局研究包括机械通气的需要和全身和感染性并发症的发生率。通过相对风险估计确定与死亡相关的基线和时间依赖性危险因素。
在 2831 名入院患者中，515 名（24.3%为女性）接受了 TCZ 和类固醇治疗。有 135 人死亡（26.2%），380 人（73.8%）临床状况改善。242 名（47%）患者需要机械通气。其中，44.2%（107/242）康复并脱机。37%的患者在病房接受治疗，无需入住重症监护病房（ICU）。分别有 2.13%、2.13%和 0.06%的患者发生医院获得性肺炎、血流细菌和真菌感染等感染性并发症。年龄≥60 岁（P=0.014）、合并症如高血压（P=0.011）、白细胞介素-6≥100pg/ml（P=0.002）、D-二聚体≥1000ng/ml（P<0.0001）、CT 严重指数≥18（P<0.0001）和全身并发症如肺纤维化（P=0.019）、心律失常（P<0.0001）、低血压（P<0.0001）和脑病（P<0.0001）与死亡风险增加相关。
TCZ 和类固醇联合治疗可能安全有效治疗 COVID-19 相关细胞因子释放综合征。这种抗炎联合治疗的疗效需要在随机对照试验中验证。
