COVID-19 诱导的 ARDS 的免疫亚型和对康复血浆的反应:CONFIDENT 试验的二次分析。

IF 5.7 1区 医学 Q1 CRITICAL CARE MEDICINE Annals of Intensive Care Pub Date : 2024-10-21 DOI:10.1186/s13613-024-01392-1
Benoît Misset, Anh Nguyet Diep, Axelle Bertrand, Michael Piagnerelli, Eric Hoste, Isabelle Michaux, Elisabeth De Waele, Alexander Dumoulin, Philippe G Jorens, Emmanuel van der Hauwaert, Frédéric Vallot, Walter Swinnen, Nicolas De Schryver, Nathalie de Mey, Nathalie Layios, Jean-Baptiste Mesland, Sébastien Robinet, Etienne Cavalier, Anne-Françoise Donneau, Michel Moutschen, Pierre-François Laterre
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引用次数: 0

摘要

背景:新陈代谢血浆(CP)降低了在CONFIDENT试验中接受治疗的COVID-19诱发ARDS(C-ARDS)患者的死亡率。由于患者的免疫异质性,我们推测不同群组的患者对 CP 的治疗反应可能不同:方法:我们使用多重技术测量了 20 种细胞因子、趋化因子和细胞粘附标记物,这些标记物是在患者加入 CONFIDENT 试验时测量的。我们进行了描述性统计、无监督分层聚类分析,并研究了聚类与 CP 对第 28 天死亡率影响之间的关联:在 CONFIDENT 纳入的 475 例患者中,有 391 例(82%)被抽样,196/391 例(50.1%)被分配到 CP。我们确定了四种亚型,分别代表 89 例(22.8%)、178 例(45.5%)、38 例(9.7%)和 86 例(22.0%)患者。主成分分析中贡献最大的生物标记物是 IL-1β、IL-12p70、IL-6、IFN-α、IL-17A、IFN-γ、IL-13、TFN-α、总 IgG 和 CXCL10。亚表型-1显示较低的免疫反应,亚表型-2显示较高的适应性反应,亚表型-3显示最高的先天性抗病毒、促炎和抗炎反应以及粘附分子活化,亚表型-4显示较高的促炎和抗炎反应、迁移蛋白和粘附分子活化。亚表型-2 和亚表型-4 在纳入时的严重程度较高。在每个亚型中,CP治疗对死亡率的影响似乎都高于标准治疗,亚型之间没有异质性(P = 0.97):结论:在C-ARDS患者中,我们根据其免疫反应确定了4种亚型。这些亚型与不同的临床特征相关。试验注册:试验注册:列日大学医院伦理委员会 CE 2020/239.Clinicaltrials:gov NCT04558476。注册时间:2020-09-11,https://www.Clinicaltrials: gov/study/NCT04558476 。
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Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial.

Background: Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP.

Methods: We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality.

Results: Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97).

Conclusion: In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes.

Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239.

Clinicaltrials: gov NCT04558476. Registered 2020-09-11, https://www.

Clinicaltrials: gov/study/NCT04558476 .

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来源期刊
Annals of Intensive Care
Annals of Intensive Care CRITICAL CARE MEDICINE-
CiteScore
14.20
自引率
3.70%
发文量
107
审稿时长
13 weeks
期刊介绍: Annals of Intensive Care is an online peer-reviewed journal that publishes high-quality review articles and original research papers in the field of intensive care medicine. It targets critical care providers including attending physicians, fellows, residents, nurses, and physiotherapists, who aim to enhance their knowledge and provide optimal care for their patients. The journal's articles are included in various prestigious databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, OCLC, PubMed, PubMed Central, Science Citation Index Expanded, SCOPUS, and Summon by Serial Solutions.
期刊最新文献
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