IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Institut Régional du Cancer de Montpellier, Université de Montpellier, Montpellier, France.
Department of Biochemistry and Hormonology, INSERM, CNRS, University Hospital Center of Montpellier, University of Montpellier, PhyMedExp, Montpellier, France.
J Med Virol. 2023 Jan;95(1):e28209. doi: 10.1002/jmv.28209. Epub 2022 Oct 31.
In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.
在疫情早期,我们率先提出中性粒细胞胞外诱捕网(NETs)在 COVID-19 发病机制中发挥关键作用。这项基于 279 人的探索性前瞻性研究表明,非重症(NS)、重症(S)和急性后期(PAP)COVID-19 患者的血浆中性粒细胞弹性蛋白酶、髓过氧化物酶和核与线粒体来源的循环 DNA 水平与健康个体相比存在统计学差异,并揭示了这些 NETs 标志物在疾病严重程度方面的高诊断能力。通过接受者操作特征曲线(AUROC)确定的 NE、MPO 和 cir-nDNA 的诊断能力分别为 0.95、0.99 和 0.94,0.97、1.0 和 0.82,以及 0.64、1.0 和 0.93,分别在 NS、S 和 PAP 患者亚组中。此外,相当一部分 NS、S 和 PAP 患者表现出 aCL IgM/IgG 和抗 B2GP IgM/IgG 阳性。我们首次证明这些 NETs 标志物在 PAP 患者中持续存在,继而持续存在固有免疫反应失衡,以及低水平的持续促血栓形成潜在活性,这突出表明需要监测所有 COVID-19 PAP 个体的这些标志物,以研究重症监护后的急性后期 COVID-19 发病机制,并更好地确定哪些医疗资源将确保患者完全康复。