Hypercoagulable state and thromboembolic complications are potential life-threatening events in COVID-19 patients. Our previous studies demonstrated that SARS-CoV-2 infection as well as viral spike protein expressed epithelial cells exhibit senescence with the release of inflammatory molecules, including alarmins. We observed extracellular alarmins present in the culture media of SARS-CoV-2 spike expressing cells activate human THP-1 monocytes to secrete pro-inflammatory cytokines to a significant level. The release of THP-1 derived pro-inflammatory cytokine signature correlated with the serum of acute COVID-19 patient, but not in post-COVID-19 state. Our study suggested that the alarmins secreted by spike expressing cells, initiated phagocytosis property of THP-1 cells. The phagocytic monocytes secreted complement component C5a and generated an autocrine signal via C5aR1 receptor. The C5a-C5aR1 signal induced formation of monocyte mediated extracellular trap resulted in the generation of a prothrombogenic stimulus with activating platelets and increased tissue factor activity. We also observed an enhanced C5a level, platelet activating factor, and high tissue factor activity in the serum of acute COVID-19 patients, but not in recovered patients. Our present study demonstrated that SARS-CoV-2 spike protein modulates monocyte responses in a paracrine manner for prothrombogenic stimulus by the generation of C5a complement component.

中文翻译：

---

SARS-CoV-2 刺突蛋白对人单核细胞 THP-1 细胞活化和代表严重 COVID-19 的促血栓形成刺激启动的旁观者效应

高凝状态和血栓栓塞并发症是 COVID-19 患者潜在的危及生命的事件。我们之前的研究表明，SARS-CoV-2 感染以及病毒刺突蛋白表达的上皮细胞随着炎症分子（包括警报素）的释放而出现衰老。我们观察到存在于 SARS-CoV-2 刺突表达细胞培养基中的细胞外警报素激活人 THP-1 单核细胞以显着水平分泌促炎细胞因子。THP-1 衍生的促炎细胞因子特征的释放与急性 COVID-19 患者的血清相关，但与 COVID-19 后状态无关。我们的研究表明，刺突表达细胞分泌的警报素启动了 THP-1 细胞的吞噬作用。吞噬单核细胞分泌补体成分 C5a 并通过 C5aR1 受体产生自分泌信号。C5a-C5aR1 信号诱导形成单核细胞介导的细胞外陷阱，导致产生具有活化血小板和增加的组织因子活性的促血栓形成刺激物。我们还观察到急性 COVID-19 患者血清中 C5a 水平、血小板活化因子和组织因子活性升高，但在康复患者中没有观察到。我们目前的研究表明，SARS-CoV-2 刺突蛋白通过 C5a 补体成分的产生以旁分泌方式调节单核细胞对促血栓形成刺激的反应。C5a-C5aR1 信号诱导形成单核细胞介导的细胞外陷阱，导致产生具有活化血小板和增加的组织因子活性的促血栓形成刺激物。我们还观察到急性 COVID-19 患者血清中 C5a 水平、血小板活化因子和组织因子活性升高，但在康复患者中没有观察到。我们目前的研究表明，SARS-CoV-2 刺突蛋白通过 C5a 补体成分的产生以旁分泌方式调节单核细胞对促血栓形成刺激的反应。C5a-C5aR1 信号诱导形成单核细胞介导的细胞外陷阱，导致产生具有活化血小板和增加的组织因子活性的促血栓形成刺激物。我们还观察到急性 COVID-19 患者血清中 C5a 水平、血小板活化因子和组织因子活性升高，但在康复患者中没有观察到。我们目前的研究表明，SARS-CoV-2 刺突蛋白通过 C5a 补体成分的产生以旁分泌方式调节单核细胞对促血栓形成刺激的反应。