Abstract Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.

中文翻译：

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COVID-19细胞因子风暴：炎症的愤怒


摘要 需要入住 ICU 的 COVID-19 患者可能会出现细胞因子风暴。它是多种炎症细胞因子释放失控的状态。细胞因子风暴的分子机制尚未得到广泛探索。 SARS-CoV-2 刺突糖蛋白与作为其细胞受体的血管紧张素转换酶 2 (ACE2) 的结合会触发复杂的分子事件，从而导致过度炎症。这项工作解决了可能与 SARS-CoV-2 驱动的炎症细胞因子过度产生有关的四个分子轴。病毒介导的 ACE2 下调通过肾素-血管紧张素-醛固酮系统（ACE/血管紧张素 II/AT1R 轴）失调、Mas 受体（ACE2/MasR 轴）减弱、 [des-Arg9]-缓激肽（ACE2/缓激肽 B1R/DABK 轴），以及补体系统（包括 C5a 和 C5b-9 成分）的激活。这些轴的分子澄清将阐明一系列应对细胞因子风暴的治疗策略，以预防和治疗与 COVID-19 相关的急性呼吸窘迫综合征。