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托珠单抗治疗 5 例 SARS-CoV-2 导致早期 ARDS 的实体和复合组织移植受者。

Tocilizumab therapy in 5 solid and composite tissue transplant recipients with early ARDS due to SARS-CoV-2.

机构信息

Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio.

Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio.

出版信息

Am J Transplant. 2020 Nov;20(11):3191-3197. doi: 10.1111/ajt.16080. Epub 2020 Jul 22.

Abstract

There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID-19) in solid organ transplant recipients but negligible data-driven guidance on clinical management. A biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), beginning with a flu-like illness followed by an intense inflammatory response characterized by elevated c-reactive protein (CRP), interleukin 6 (IL-6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL-6. Tocilizumab is an IL-6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T-cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS-CoV-2-related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS-CoV-2-related ARDS that received tocilizumab with favorable short-term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population.

摘要

有一些新兴数据描绘了实体器官移植受者中 2019 年冠状病毒病(COVID-19)的临床特征,但关于临床管理的具体数据指导却很少。一些感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的患者出现了双相病程,最初表现为类似流感的疾病,随后出现强烈的炎症反应,表现为 C 反应蛋白(CRP)、白细胞介素 6(IL-6)升高和急性呼吸窘迫综合征(ARDS),死亡率较高。这种过度和可能失调的免疫反应促使人们对靶向相关细胞因子的治疗药物产生了兴趣,特别是白细胞介素 6(IL-6)。托珠单抗是一种白细胞介素 6 受体拮抗剂,在各种风湿性疾病和嵌合抗原受体 T 细胞疗法引起的细胞因子释放综合征中都有使用记录,但在实体器官和复合组织移植受者(SOT/CTTRs)中,SARS-CoV-2 相关 ARDS 应用托珠单抗的经验尚未详细报道。我们报告了 5 例 SOT/CTTRs 中 SARS-CoV-2 相关 ARDS 患者接受托珠单抗治疗的临床过程,其中 4 例患者的短期预后良好。反应的特征是 CRP 降低、停止使用升压药、氧合和呼吸力学改善以及呼吸机支持的时间长短不一。在托珠单抗给药后 2 周内发生了 4 例细菌感染。我们讨论了安全性问题以及需要进行随机对照试验来明确托珠单抗在该人群中的临床应用价值。

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