Clinical Medical Research Center, Southwest Hospital, Army Military Medical University, Chongqing, China.
Front Immunol. 2022 Mar 2;13:838011. doi: 10.3389/fimmu.2022.838011. eCollection 2022.
Infection with SARS-CoV-2, the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism of COVID-19 immunopathy is the recruitment and activation of neutrophils at the infection site, which also predicts disease severity and poor outcomes. The release of neutrophil extracellular traps (NETs), occurring during a regulated form of neutrophil cell death known as NETosis, is a key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis and NET generation have been observed in the neutrophils of many COVID-19 patients, leading to unfavorable coagulopathy and immunothrombosis. Moreover, excessive NETosis and NET generation are now more widely recognized as mediators of additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes of NET-producing neutrophils (e.g., low-density granulocytes) and explain the biological importance of NETs and the protein cargos of NETs in COVID-19. In addition, we discuss the mechanisms by which SARS-CoV-2 causes NETosis by upregulating viral processes (e.g., viral entry and replication) as well as host pro-NET mechanisms (e.g., proinflammatory mediator release, platelet activation, and autoantibody production). Furthermore, we provide an update of the main findings of NETosis and NETs in immunothrombosis and other COVID-19-related disorders, such as aberrant immunity, neurological disorders, and post COVID-19 syndromes including lung fibrosis, neurological disorder, tumor progression, and deteriorated chronic illness. Finally, we address potential prospective COVID-19 treatment strategies that target dysregulated NETosis and NET formation inhibition of NETosis and promotion of NET degradation, respectively.
感染导致 2019 年冠状病毒病（COVID-19）大流行的 SARS-CoV-2 会引起呼吸道问题和多器官功能障碍。COVID-19 免疫病理学的一个关键机制是感染部位中性粒细胞的募集和激活，这也预测了疾病的严重程度和不良结局。中性粒细胞细胞外陷阱（NETs）的释放，发生在一种称为 NETosis 的受调控的中性粒细胞死亡形式中，是介导中性粒细胞引起的有害作用的关键效应功能。在许多 COVID-19 患者的中性粒细胞中观察到大量的 NETosis 和 NET 的产生，导致不良的凝血功能障碍和免疫血栓形成。此外，过度的 NETosis 和 NET 的产生现在被更广泛地认为是继 SARS-CoV-2 感染后引起其他病理生理异常的介质。在这篇小综述中，我们介绍了产生 NET 的中性粒细胞的亚型（例如低密度粒细胞），并解释了 NETs 的生物学重要性以及 NETs 中的蛋白载物在 COVID-19 中的作用。此外，我们讨论了 SARS-CoV-2 通过上调病毒过程（例如病毒进入和复制）以及宿主促 NET 机制（例如促炎介质释放、血小板激活和自身抗体产生）引起 NETosis 的机制。此外，我们提供了 NETosis 和 NET 在免疫血栓形成和其他 COVID-19 相关疾病中的主要发现的最新进展，例如异常免疫、神经紊乱以及 COVID-19 后综合征，包括肺纤维化、神经紊乱、肿瘤进展和慢性疾病恶化。最后，我们讨论了针对失调的 NETosis 和 NET 形成的潜在 COVID-19 治疗策略，分别为 NETosis 的抑制和 NET 的降解。
