CHU Bordeaux, Medical Intensive Care Unit, Pessac, France.
Univ. Bordeaux, INSERM, U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Pessac, France.
Front Immunol. 2022 Mar 17;13:851497. doi: 10.3389/fimmu.2022.851497. eCollection 2022.
Coronavirus disease 2019 (COVID-19) can cause life-threatening acute respiratory distress syndrome (ARDS). Recent data suggest a role for neutrophil extracellular traps (NETs) in COVID-19-related lung damage partly due to microthrombus formation. Besides, pulmonary embolism (PE) is frequent in severe COVID-19 patients, suggesting that immunothrombosis could also be responsible for increased PE occurrence in these patients. Here, we evaluate whether plasma levels of NET markers measured shorty after admission of hospitalized COVID-19 patients are associated with clinical outcomes in terms of clinical worsening, survival, and PE occurrence.
Ninety-six hospitalized COVID-19 patients were included, 50 with ARDS (severe disease) and 46 with moderate disease. We collected plasma early after admission and measured 3 NET markers: total DNA, myeloperoxidase (MPO)-DNA complexes, and citrullinated histone H3. Comparisons between survivors and non-survivors and patients developing PE and those not developing PE were assessed by Mann-Whitney test.
Analysis in the whole population of hospitalized COVID-19 patients revealed increased circulating biomarkers of NETs in patients who will die from COVID-19 and in patients who will subsequently develop PE. Restriction of our analysis in the most severe patients, i.e., the ones who enter the hospital for COVID-19-related ARDS, confirmed the link between NET biomarker levels and survival but not PE occurrence.
Our results strongly reinforce the hypothesis that NETosis is an attractive therapeutic target to prevent COVID-19 progression but that it does not seem to be linked to PE occurrence in patients hospitalized with COVID-19.
2019 年冠状病毒病(COVID-19)可导致危及生命的急性呼吸窘迫综合征(ARDS)。最近的数据表明,中性粒细胞胞外陷阱(NETs)在 COVID-19 相关肺损伤中起作用,部分原因是微血栓形成。此外,严重 COVID-19 患者中肺栓塞(PE)很常见,这表明免疫血栓形成也可能是这些患者中 PE 发生率增加的原因。在这里,我们评估了住院 COVID-19 患者入院后短期测量的血浆 NET 标志物水平与临床恶化、生存和 PE 发生的临床结局是否相关。
共纳入 96 例住院 COVID-19 患者,其中 50 例为 ARDS(重症),46 例为中度疾病。我们在入院后早期采集血浆,并测量了 3 种 NET 标志物:总 DNA、髓过氧化物酶(MPO)-DNA 复合物和瓜氨酸化组蛋白 H3。通过 Mann-Whitney 检验比较幸存者和非幸存者以及发生 PE 和未发生 PE 的患者。
在住院 COVID-19 患者的整个人群中进行分析显示,死于 COVID-19 的患者和随后发生 PE 的患者循环 NETs 的生物标志物增加。将我们的分析限制在最严重的患者(即因 COVID-19 相关 ARDS 入院的患者)中,证实了 NET 生物标志物水平与生存之间的联系,但与 PE 的发生无关。
我们的研究结果强烈支持 NETosis 是预防 COVID-19 进展的有吸引力的治疗靶点的假设,但它似乎与住院 COVID-19 患者的 PE 发生无关。