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
{"title":"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。","authors":"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","doi":"10.1186/s13613-024-01392-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Ethics Committee of the University Hospital of Liège CE 2020/239.</p><p><strong>Clinicaltrials: </strong>gov NCT04558476. Registered 2020-09-11, https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT04558476 .</p>","PeriodicalId":7966,"journal":{"name":"Annals of Intensive Care","volume":"14 1","pages":"160"},"PeriodicalIF":5.7000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493925/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial.\",\"authors\":\"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\",\"doi\":\"10.1186/s13613-024-01392-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Ethics Committee of the University Hospital of Liège CE 2020/239.</p><p><strong>Clinicaltrials: </strong>gov NCT04558476. Registered 2020-09-11, https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT04558476 .</p>\",\"PeriodicalId\":7966,\"journal\":{\"name\":\"Annals of Intensive Care\",\"volume\":\"14 1\",\"pages\":\"160\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493925/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Intensive Care\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13613-024-01392-1\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Intensive Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13613-024-01392-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
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.
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.
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