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用于COVID-19肺炎中细菌感染、病毒感染和疾病进展分类的29种mRNA宿主反应特征：SAVE-MORE随机临床试验的事后分析

29-mRNA host response signatures for classification of bacterial infection, viral infection and disease progression in COVID-19 pneumonia: a post hoc analysis of the SAVE-MORE randomized clinical trial.

作者信息

Kyriazopoulou Evdoxia, Kotsaki Antigone, Safarika Asimina, Poulakou Garyfallia, Milionis Haralampos, Metallidis Simeon, Adamis Georgios, Fragkou Archontoula, Rapti Aggeliki, Del Vecchio Pierluigi, Kalomenidis Ioannis, Kitzoglou Danae, Angheben Andrea, Kainis Ilias, Iliopoulou Konstantina, Serino Francesco Saverio, Bakakos Petros, Tzavara Vassiliki, Ioannou Sofia, Dagna Lorenzo, Dimakou Katerina, Tzatzagou Glykeria, Chini Maria, Bassetti Matteo, Kotsis Vasileios, Tsoukalas George, Selmi Carlo, Nikolakopoulou Sofia, Samarkos Michael, Doumas Michael, Masgala Aikaterini, Papanikolaou Ilias, Argyraki Aikaterini, Akinosoglou Karolina, Symbardi Styliani, Panagopoulos Periklis, Dalekos George N, Liesenfeld Oliver, Sweeney Timothy E, Khatri Purvesh, Giamarellos-Bourboulis Evangelos J

机构信息

4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Intensive Care Med Exp. 2025 Jun 30;13(1):67. doi: 10.1186/s40635-025-00777-1.

DOI:10.1186/s40635-025-00777-1
PMID:40583075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12206681/
Abstract

BACKGROUND: Biomarkers based on host response signatures are currently under development for the critically ill. We applied a 29-mRNA classifier for the diagnosis and prognosis of suspected acute infection and sepsis (TriVerity, Inflammatix Inc.) in patients hospitalized with COVID-19. METHODS: We applied three scores from locked classifiers (IMX-BVN-4 and IMX-SEV-4) from the 29-mRNA TriVerity blood test in participants of the SAVE-MORE randomized clinical trial (ClinicalTrials.gov NCT04680949) at baseline and days 4 and 7 of treatment, to classify bacterial infection, viral infection and decompensation. Participants were adults hospitalized with confirmed COVID-19 pneumonia and plasma soluble urokinase plasminogen activator receptor (suPAR) levels of ≥ 6 ng/ml, randomized to placebo or anakinra treatment. RESULTS: A total of 471 patients were studied. At baseline nearly 90% had a Very Low or Low IMX-BVN-4 Bacterial Score and Moderate, High or Very High IMX-BVN-4 Viral Score. Anakinra treatment had an effect on the expression of genes indicating IMX-SEV-4 High or Very High scores after a 7 day treatment compared to baseline (12.9% of anakinra-treated patients continued being classified as high severity vs 20.4% of placebo-treated patients, p 0.046). CONCLUSIONS: The classifiers were well tested in COVID-19 pneumonia and may become a useful tool for hospitalized patients.

摘要

背景：基于宿主反应特征的生物标志物目前正在为重症患者研发。我们将一种29-mRNA分类器应用于新冠病毒病（COVID-19）住院患者疑似急性感染和脓毒症的诊断及预后评估（TriVerity，Inflammatix公司）。 方法：我们在SAVE-MORE随机临床试验（ClinicalTrials.gov标识符：NCT04680949）的参与者中，于基线期以及治疗第4天和第7天应用了来自29-mRNA TriVerity血液检测的锁定分类器（IMX-BVN-4和IMX-SEV-4）的三个评分，以对细菌感染、病毒感染和失代偿进行分类。参与者为确诊COVID-19肺炎且血浆可溶性尿激酶型纤溶酶原激活物受体（suPAR）水平≥6 ng/ml的住院成人，随机分为接受安慰剂或阿那白滞素治疗。 结果：共研究了471例患者。在基线期，近90%的患者IMX-BVN-4细菌评分为极低或低，IMX-BVN-4病毒评分为中度、高或极高。与基线相比，阿那白滞素治疗7天后对指示IMX-SEV-4高或极高评分的基因表达有影响（接受阿那白滞素治疗的患者中有12.9%继续被分类为高严重度，而接受安慰剂治疗的患者中为20.4%，p = 0.046）。 结论：这些分类器在COVID-19肺炎中得到了充分验证，可能成为住院患者的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/e2377d69f663/40635_2025_777_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/c4d03b8fc095/40635_2025_777_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/e8b92cb7fecc/40635_2025_777_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/e2377d69f663/40635_2025_777_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/c4d03b8fc095/40635_2025_777_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/e8b92cb7fecc/40635_2025_777_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4415/12206681/e2377d69f663/40635_2025_777_Fig3_HTML.jpg

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29-mRNA host response signatures for classification of bacterial infection, viral infection and disease progression in COVID-19 pneumonia: a post hoc analysis of the SAVE-MORE randomized clinical trial.

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本文引用的文献

[1]
From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations for Developing Precision Medicine in the ICU.

Am J Respir Crit Care Med. 2024-7-15

[2]
Multisite validation of a host response signature for predicting likelihood of bacterial and viral infections in patients with suspected influenza.

Eur J Clin Invest. 2023-5

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Using a 29-mRNA Host Response Classifier To Detect Bacterial Coinfections and Predict Outcomes in COVID-19 Patients Presenting to the Emergency Department.

Microbiol Spectr. 2022-12-21

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A 29-MRNA HOST RESPONSE WHOLE-BLOOD SIGNATURE IMPROVES PREDICTION OF 28-DAY MORTALITY AND 7-DAY INTENSIVE CARE UNIT CARE IN ADULTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH SUSPECTED ACUTE INFECTION AND/OR SEPSIS.

Shock. 2022-9-1

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Open Forum Infect Dis. 2022-8-25

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Intensive Care Med. 2022-9

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Eur J Emerg Med. 2022-10-1

[10]
Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial.

Nat Med. 2021-10

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