Clinical Sciences, Clinical Development and Medical Affairs, Biocon Biologics India Ltd , Bengaluru, India.
Consultant, Joshi Clinic and Lilavati Hospital , Mumbai, India.
Expert Opin Biol Ther. 2020 Sep;20(9):1025-1031. doi: 10.1080/14712598.2020.1798399. Epub 2020 Jul 29.
The globally rampant SARS CoV-2 pandemic requires novel medical strategies to control the severity of disease and death due to complications. Of the 15-20% patients that develop pulmonary symptoms, a sub-set develops an acute respiratory distress syndrome (ARDS) rapidly progressing into a critical condition. Marked elevation of cytokines/chemokines is observed with elevation of additional markers of inflammation, coagulation, and organ damage such as CRP, D-dimer, LDH, Ferritin and Troponin-I. This hyperinflammation leads to worsening of oxygen saturation due to pulmonary infiltration and exudation, organ damage, and dysfunction of coagulation pathway and may lead to multi-organ failure.
The role of anti-inflammatory monoclonal antibodies such as Itolizumab, in cytokine storm.
Itolizumab, an mAb, binds to domain-1 of CD-6 that is responsible for priming, activation, and differentiation of T-cells. Itolizumab significantly reduces T-cell proliferation along with substantial downregulation of the production of cytokines/chemokines. Approved for moderate to severe chronic plaque psoriasis in 2013 it is currently being studied for addressing COVID-19 related cytokine storm and its complications. This article reviews its use in COVID-19 infections; its dose, administration protocol, contra-indications, and safety in treating moderate-to-severe ARDS by preventing and treating the cytokine storm and its complications.
由于并发症,全球肆虐的严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)大流行需要新的医学策略来控制疾病和死亡的严重程度。在出现肺部症状的 15%-20%患者中,有一部分会迅速发展为急性呼吸窘迫综合征(ARDS),进而发展为危急状态。观察到细胞因子/趋化因子明显升高,同时还伴有炎症、凝血和器官损伤的其他标志物升高,如 CRP、D-二聚体、LDH、铁蛋白和肌钙蛋白 I。这种过度炎症会导致氧饱和度因肺部浸润和渗出、器官损伤以及凝血途径功能障碍而恶化,并可能导致多器官衰竭。
抗细胞因子单克隆抗体(如 Itolizumab)在细胞因子风暴中的作用。
Itolizumab 是一种 mAb,与负责 T 细胞初始激活、分化的 CD-6 结构域 1 结合。Itolizumab 可显著抑制 T 细胞增殖,同时显著下调细胞因子/趋化因子的产生。2013 年,Itolizumab 被批准用于治疗中度至重度慢性斑块型银屑病,目前正在研究其在治疗 COVID-19 相关细胞因子风暴及其并发症中的作用。本文综述了 Itolizumab 在 COVID-19 感染中的应用;其剂量、给药方案、禁忌证以及通过预防和治疗细胞因子风暴及其并发症治疗中度至重度 ARDS 的安全性。