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.

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，