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Future perspective: biologic agents in patients with severe COVID-19.
Immunopharmacology and Immunotoxicology ( IF 2.9 ) Pub Date : 2020-09-14 , DOI: 10.1080/08923973.2020.1818770
Arzu Didem Yalcin,Ata Nevzat Yalcin

Abstract

The SARS-CoV-2 is a β-CoV, which is enveloped by non-segmented positive-stranded RNA virüs. When β-CoV infects the respiratory tract, it can cause mild and/or severe acute respiratory syndrome (SARS) with consequent release of cytokines/mediators, including interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-10, IP10, IL-12, IL-13, IL-17, IL-33, IL-25, IL-37, IL-38, GCSF, GM-CSF, HGF, IP-10, MCP-1, MIP-1α (also known as CCL3), IFN-γ, IFN-α, TRAIL, MCSF, and TNF-α. Our hypothesis of writing this article can be summarized as; if the monoclonal antibody (mAb) administered by us does not inhibit the immune response for the β-CoV and inhibits uncontrolled-adaptive/hyperimmune responses (also called cytokine storm) on endothelium level, then it may cause severe coronavirus disease 2019 (COVID-19). Anakinra is a human IL-1 receptor antagonist. By inhibiting IL-1α/IL-1β competitively from binding to the IL-1 type-I receptor, anakinra, neutralizes the activity that pertains to these key mediators of autoinflammatory and/or immune processes. Tocilizumab is a blocker of IL-6R that can effectively block IL-6 signal transduction pathway. Omalizumab that binds to the CH3 domain is near to the binding site for the high-affinity IgE Fc receptors type-I of human IgE. Myocardial, lung and hepatorenal injury in patients with COVID-19 could be due to cytokine storm, hypoxic injury, or/and direct endothelial/vascular injury. We propose combination of mAbs with remdesivir and/or favipiravir in severe COVID-19 cases, such as septic shock, acute respiratory deficiency syndrome, and/or multiple organ failure. Finally, we highlight the therapeutic mAbs that target patients with severe COVID-19.



中文翻译:

未来前景:重度COVID-19患者的生物制剂。

摘要

SARS-CoV-2是一种β-CoV,被非分段的正链RNA病毒包裹。当β-CoV感染呼吸道时,会引起轻度和/或严重的急性呼吸道综合症(SARS),并随后释放出细胞因子/介体,包括白介素(IL)-1β,IL-2,IL-4,IL-5 ,IL-6,IL-7,IL-8(CXCL8),IL-10,IP10,IL-12,IL-13,IL-17,IL-33,IL-25,IL-37,IL-38, GCSF,GM-CSF,HGF,IP-10,MCP-1,MIP-1α(也称为CCL3),IFN-γ,IFN-α,TRAIL,MCSF和TNF-α。我们撰写本文的假设可以概括为:如果我们施用的单克隆抗体(mAb)在内皮水平上不抑制β-CoV的免疫反应并抑制不受控制的适应性/超免疫反应(也称为细胞因子风暴),则可能会导致2019年的严重冠状病毒病19)。Anakinra是人IL-1受体拮抗剂。anakinra通过竞争性抑制IL-1α/IL-1β与IL-1 I型受体的结合,中和了与自身炎症和/或免疫过程的这些关键介质有关的活性。托珠单抗是IL-6R的阻断剂,可以有效阻断IL-6信号转导途径。与CH3域结合的奥马珠单抗靠近人IgE的I型高亲和力IgE Fc受体的结合位点。COVID-19患者的心肌,肺和肝肾损伤可能是由于细胞因子风暴,低氧损伤或/和直接内皮/血管损伤所致。我们建议在重度COVID-19病例(如败血性休克,急性呼吸系统综合症和/或多器官功能衰竭)中,将mAbs与瑞贝昔韦和/或法维吡韦联合使用。最后,

更新日期:2020-09-14
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