中性粒细胞胞外捕获物与 COVID-19 严重程度之间的实际关系是什么？纵向研究

IF 4.7 2区医学 Q1 RESPIRATORY SYSTEM

Respiratory Research Pub Date : 2024-01-19 DOI:10.1186/s12931-023-02650-9

Cristina de Diego, Ana Belén Lasierra, Lucía López-Vergara, Laura Torralba, Pablo Ruiz de Gopegui, Raquel Lahoz, Claudia Abadía, Javier Godino, Alberto Cebollada, Beatriz Jimeno, Carlota Bello, Antonio Tejada, Salvador Bello

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引用次数: 0

摘要

中性粒细胞胞外陷阱（NET）多次被认为与 COVID-19 的严重程度和死亡率有关。然而，关于NET的定量还没有达成共识，关于其在疾病期间的演变情况的数据也很少。我们对 COVID-19 患者住院期间的循环 NET 标记物进行了研究。我们前瞻性地纳入了 93 名患者（201 份血样），评估了 3 个演变阶段（病毒、早期和晚期炎症）的疾病严重程度。其中 72 人在不同阶段共采集了 180 份样本。我们还对 55 名年龄、性别和合并症相似的对照组进行了评估。我们测量了血清中的 4 种 NET 标志物：cfDNA、CitH3、MPO-DNA 和 NE-DNA 复合物；以及中性粒细胞相关细胞因子 IL-8 和 G-CSF。在整个住院期间，COVID-19 组的 CitH3（28.29 vs 20.29 pg/mL，p = 0.022）、cfDNA、MPO-DNA 和 NE-DNA（7.87 vs 2.56 ng/mL；分别为 0.80 vs 0.52 和 1.04 vs 0.72，p < 0.001）均高于对照组。只有 cfDNA 是死亡率和重症监护需求的独立风险因素。中性粒细胞计数、IL-8和G-CSF与严重程度显著相关。MPO-DNA和NE-DNA显示出显著的相关性（r：0.483，p＜0.001），包括所有3个阶段和所有严重程度等级，只有在进化的第10-16天，死亡患者的MPO-DNA和NE-DNA仍显著较高。其他NET标志物之间的相关性低于预期。COVID-19患者在整个住院期间都存在NET的循环生物标志物，cfDNA与病情严重程度和死亡率相关，但其他三种标志物与这些结果几乎没有关联。中性粒细胞活性和中性粒细胞计数也与病情严重程度有关。MPO-DNA和NE-DNA能更好地反映NET的形成。cfDNA似乎与整体组织损伤更相关；以前广泛使用该标记物可能会高估NET与严重程度之间的关系。目前，NET标记物的精确测量还存在局限性，因此很难评估其在COVID-19发病机制中的真正作用。

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What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study

Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, and there are scarce data on their evolution during the disease. We studied circulating NET markers in patients with COVID-19 throughout their hospitalization. We prospectively included 93 patients (201 blood samples), evaluating the disease severity in 3 evolutionary phases (viral, early, and late inflammation). Of these, 72 had 180 samples in various phases. We also evaluated 55 controls with similar age, sex and comorbidities. We measured 4 NET markers in serum: cfDNA, CitH3, and MPO-DNA and NE-DNA complexes; as well as neutrophil-related cytokines IL-8 and G-CSF. The COVID-19 group had higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), and cfDNA, MPO-DNA, and NE-DNA (7.87 vs 2.56 ng/mL; 0.80 vs 0.52 and 1.04 vs 0.72, respectively, p < 0.001 for all) than the controls throughout hospitalisation. cfDNA was the only NET marker clearly related to severity, and it remained higher in non-survivors during the 3 phases. Only cfDNA was an independent risk factor for mortality and need for intensive care. Neutrophil count, IL-8, and G-CSF were significantly related to severity. MPO-DNA and NE-DNA showed significant correlations (r: 0.483, p < 0.001), including all 3 phases and across all severity grades, and they only remained significantly higher on days 10–16 of evolution in those who died. Correlations among the other NET markers were lower than expected. The circulating biomarkers of NETs were present in patients with COVID-19 throughout hospitalization. cfDNA was associated with severity and mortality, but the three other markers showed little or no association with these outcomes. Neutrophil activity and neutrophil count were also associated with severity. MPO-DNA and NE-DNA better reflected NET formation. cfDNA appeared to be more associated with overall tissue damage; previous widespread use of this marker could have overestimated the relationship between NETs and severity. Currently, there are limitations to accurate NET markers measurement that make it difficult to assess its true role in COVID-19 pathogenesis.

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来源期刊

Respiratory Research 医学-呼吸系统

自引率

1.70%

发文量

314

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.