An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.

中文翻译：

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致命性 COVID-19 相关肺损伤中的中性粒细胞胞外陷阱

中性粒细胞胞外陷阱 (NETs) 的过度形成，以前被证明与细胞因子风暴和急性呼吸窘迫综合征 (ARDS) 具有普遍的内皮功能障碍和血栓形成密切相关，已被认为是影响病理生理学和临床表现的核心因素。严重的 COVID-19。越来越多的血清学和形态学证据增加了这一假设，也涉及潜在的治疗方案。在这项研究中，我们使用免疫组织化学和组织化学来追踪 7 名 COVID-19 患者尸体解剖肺组织中的 NET 及其分子标记。关键免疫形态学特征的量化能够与非 COVID-19 弥漫性肺泡损伤进行比较。我们的结果加强并扩展了最近的发现，证实 NETs 大量存在于严重受损的 COVID-19 肺组织中，特别是与肺泡毛细血管的微血栓有关。此外，我们提供的证据表明，特别容易发生 NETosis 的低密度中性粒细胞 (LDN)，在总体上对 COVID-19 相关的肺损伤，特别是血管阻塞有很大贡献。