Mastroianni Antonio, Greco Sonia, Apuzzo Giovanni, De Santis Salvatore, Oriolo Carmela, Zanolini Alfredo, Chidichimo Luciana, Vangeli Valeria
Infectious Diseases Unit, Annunziata Hospital, Viale della Repubblica s.n.c., 87100 Cosenza, Italy.
Hospital Pharmacy, Annunziata Hospital, Cosenza, Italy.
EClinicalMedicine. 2020 Jul 1;24:100410. doi: 10.1016/j.eclinm.2020.100410. eCollection 2020 Jul.
Patients with severe coronavirus disease 2019 (COVID-19) have elevated levels of acute phase reactants and inflammatory cytokines, including interleukin-6, indicative of cytokine release syndrome (CRS). The interleukin-6 receptor inhibitor tocilizumab is used for the treatment of chimeric antigen receptor T-cell therapy-induced CRS.
Patients aged 18 years or older with laboratory-confirmed COVID-19 admitted to the Annunziata Hospital in Cosenza, Italy, through March 7, 2020, who received at least one dose of tocilizumab 162 mg subcutaneously for the treatment of COVID-19-related CRS in addition to standard care were included in this retrospective observational study. The primary observation was the incidence of grade 4 CRS after tocilizumab treatment. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations.
Twelve patients were included; all had fever, cough, and fatigue at presentation, and all had at least one comorbidity (hypertension, six patients; diabetes, five patients; chronic obstructive lung disease, four patients). Seven patients received high-flow nasal cannula oxygen therapy and five received non-invasive mechanical ventilation for lung complications of COVID-19. No incidence of grade 4 CRS was observed within 1 week of tocilizumab administration in all 12 patients (100%) and within 2 days of tocilizumab administration in 5 patients (42%). The predominant pattern on chest CT scans at presentation was ground-glass opacity, air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura. Follow-up CT scans 7 to 10 days after tocilizumab treatment showed improvement of lung manifestations in all patients. No adverse events or new safety concerns attributable to tocilizumab were reported.
Tocilizumab administered subcutaneously to patients with COVID-19 and CRS is a promising treatment for reduction in disease activity and improvement in lung function. The effect of tocilizumab should be confirmed in a randomised controlled trial.
2019年冠状病毒病（COVID-19）重症患者的急性期反应物和炎性细胞因子水平升高，包括白细胞介素-6，提示细胞因子释放综合征（CRS）。白细胞介素-6受体抑制剂托珠单抗用于治疗嵌合抗原受体T细胞疗法诱导的CRS。
本回顾性观察性研究纳入了2020年3月7日前入住意大利科森扎安农齐亚塔医院、年龄在18岁及以上、实验室确诊为COVID-19、除标准治疗外还接受至少一剂162mg皮下注射托珠单抗治疗COVID-19相关CRS的患者。主要观察指标是托珠单抗治疗后4级CRS的发生率。评估胸部计算机断层扫描（CT）以研究肺部表现。
纳入12例患者；所有患者就诊时均有发热、咳嗽和疲劳症状，且均至少有一种合并症（高血压，6例；糖尿病，5例；慢性阻塞性肺疾病，4例）。7例患者接受了高流量鼻导管给氧治疗，5例患者因COVID-19肺部并发症接受了无创机械通气。所有12例患者（100%）在托珠单抗给药后1周内以及5例患者（42%）在托珠单抗给药后2天内均未观察到4级CRS的发生。就诊时胸部CT扫描的主要表现为磨玻璃影、空气支气管征、小叶间或小叶间隔光滑或不规则增厚以及相邻胸膜增厚。托珠单抗治疗后7至10天的随访CT扫描显示所有患者的肺部表现均有改善。未报告与托珠单抗相关的不良事件或新的安全问题。
对COVID-19和CRS患者皮下注射托珠单抗是一种有前景的治疗方法，可降低疾病活动度并改善肺功能。托珠单抗的疗效应在随机对照试验中得到证实。
