Abstract The COVID-19 pandemic has led to twin public health and economic crises around the world. Not only has it cost hundreds of thousands of lives but also severely impacted livelihoods and placed enormous strain on community healthcare and welfare services. In this review, we explore the events associated with SARS-CoV-2 pathogenesis and host immunopathological reactivity due to the clinical manifestations of this coronavirus infection. We discuss that the metallopeptidase enzyme ADAM17, also known as tumor necrosis factor-α-converting enzyme, TACE, is responsible for shedding of angiotensin-converting enzyme 2 and membrane-bound interleukin (IL)-6 receptor. This leads to elevated pro-inflammatory responses that result in cytokine storm syndrome. We argue that cytokine balance may be restored by recovering an IL-6 trans-signaling neutralizing buffer system through the mediation of recombinant soluble glycoprotein 130 and recombinant ADAM17/TACE prodomain inhibitor. This cytokine restoration, possibly combined with inhibition of SARS-CoV-2 entry as well as replication and coagulopathy, could be introduced as a novel approach to treat patients with severe COVID-19. In cases of co-morbidity, therapies related to the management of associated disease conditions could ameliorate those clinical manifestations.

中文翻译：

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恢复细胞因子平衡和抑制病毒生长的组合方法可能促进严重 COVID-19 病例的患者康复

摘要 COVID-19 大流行已导致全球范围内的双重公共卫生和经济危机。它不仅夺去了数十万人的生命，还严重影响了生计，给社区医疗和福利服务带来了巨大压力。在这篇综述中，我们探讨了与 SARS-CoV-2 发病机制相关的事件以及由于这种冠状病毒感染的临床表现而导致的宿主免疫病理学反应。我们讨论了金属肽酶 ADAM17，也称为肿瘤坏死因子-α-转换酶，TACE，负责血管紧张素转换酶 2 和膜结合白细胞介素 (IL)-6 受体的脱落。这会导致促炎反应升高，从而导致细胞因子风暴综合征。我们认为，通过重组可溶性糖蛋白 130 和重组 ADAM17/TACE 前域抑制剂的介导恢复 IL-6 转信号中和缓冲系统可以恢复细胞因子平衡。这种细胞因子恢复，可能与抑制 SARS-CoV-2 进入以及复制和凝血病相结合，可以作为治疗重症 COVID-19 患者的新方法引入。在合并症的情况下，与相关疾病状况管理相关的疗法可以改善这些临床表现。可以作为治疗重症 COVID-19 患者的新方法引入。在合并症的情况下，与相关疾病状况管理相关的疗法可以改善这些临床表现。可以作为治疗重症 COVID-19 患者的新方法引入。在合并症的情况下，与相关疾病状况管理相关的疗法可以改善这些临床表现。