Patients with severe coronavirus disease 2019 (COVID-19) demonstrate dysregulated immune responses including exacerbated neutrophil functions. Massive neutrophil infiltrations accompanying neutrophil extracellular trap (NET) formations are also observed in patients with severe COVID-19. However, the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation has not yet been elucidated. Here we show that 2 viral proteins encoded by SARS-CoV-2, the nucleocapsid protein and the whole spike protein, induce NET formation from neutrophils. NET formation was ROS-independent and was completely inhibited by the spleen tyrosine kinase inhibition. The inhibition of p38 MAPK, protein kinase C, and JNK signaling pathways also inhibited viral protein-induced NET formation. Our findings demonstrate one method by which SARS-CoV-2 evades innate immunity and provide a potential target for therapeutics to treat patients with severe COVID-19.

中文翻译：

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SARS-CoV-2的核衣壳蛋白和穗蛋白驱动中性粒细胞胞外陷阱形成。

患有严重冠状病毒病2019（COVID-19）的患者表现出免疫反应失调，包括嗜中性粒细胞功能加剧。在患有严重COVID-19的患者中还观察到伴随嗜中性白细胞胞外陷阱（NET）形成的大量嗜中性白细胞浸润。但是，尚未阐明严重急性呼吸综合征冠状病毒2（SARS-CoV-2）诱导的NET形成的机制。在这里，我们显示由SARS-CoV-2编码的2种病毒蛋白，核衣壳蛋白和整个刺突蛋白可诱导中性粒细胞形成NET。NET的形成不依赖ROS，并且被脾酪氨酸激酶抑制完全抑制。p38 MAPK，蛋白激酶C和JNK信号通路的抑制也抑制了病毒蛋白诱导的NET的形成。