Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial
Abstract 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,...
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2024-10-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Benoît Misset |
| collection | DOAJ |
| description | Abstract 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 . |
| format | Article |
| id | doaj-art-11cbf2802403454c91f23784e9bf64b7 |
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| publishDate | 2024-10-01 |
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| series | Annals of Intensive Care |
| spelling | doaj-art-11cbf2802403454c91f23784e9bf64b72025-08-20T02:11:55ZengSpringerOpenAnnals of Intensive Care2110-58202024-10-0114111110.1186/s13613-024-01392-1Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trialBenoît Misset0Anh Nguyet Diep1Axelle Bertrand2Michael Piagnerelli3Eric Hoste4Isabelle Michaux5Elisabeth De Waele6Alexander Dumoulin7Philippe G. Jorens8Emmanuel van der Hauwaert9Frédéric Vallot10Walter Swinnen11Nicolas De Schryver12Nathalie de Mey13Nathalie Layios14Jean-Baptiste Mesland15Sébastien Robinet16Etienne Cavalier17Anne-Françoise Donneau18Michel Moutschen19Pierre-François Laterre20Department of Intensive Care Medicine, Liège University, CHU de LiègeBiostatistic Unit, Public Health Department, Liège UniversityDepartment of Intensive Care Medicine, Liège University, CHU de LiègeDepartment of Intensive Care Medicine, Marie-Curie University Hospital, Université Libre de BruxellesDepartment of Intensive Care Medicine, University HospitalDepartment of Intensive Care, Université Catholique de Louvain, CHU UCL NamurDepartment of Clinical Nutrition, Vrije Universiteit Brussel Brussels University HospitalDepartment of Intensive Care Medicine, Delta General HospitalDepartment of Intensive Care Medicine, Antwerp University Hospital, University of Antwerp, LEMPDepartment of Intensive Care Medicine, Imelda General HospitalDepartment of Intensive Care Medicine, Wallonie Picarde General HospitalDepartment of Intensive Care Medicine, Sint Blasius General HospitalDepartment of Intensive Care Medicine, Saint-Pierre Medical ClinicDepartment of Intensive Care Medicine, OLV General HospitalDepartment of Intensive Care Medicine, Liège University, CHU de LiègeDepartment of Intensive Care Medicine, Saint-Luc University HospitalDepartment of Intensive Care Medicine, Liège University, CHU de LiègeDepartment of Clinical Chemistry, University of Liege, CIRM, CHU de LiègeBiostatistic Unit, Public Health Department, Liège UniversityDepartment of Infectious Diseases, CHU de LiègeDepartment of Intensive Care Medicine, Mons-Hainaut Regional HospitalAbstract 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 .https://doi.org/10.1186/s13613-024-01392-1COVID-19Convalescent plasmaARDSImmune responsePhenotypes |
| spellingShingle | 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 Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial Annals of Intensive Care COVID-19 Convalescent plasma ARDS Immune response Phenotypes |
| title | Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial |
| title_full | Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial |
| title_fullStr | Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial |
| title_full_unstemmed | Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial |
| title_short | Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial |
| title_sort | immunological sub phenotypes and response to convalescent plasma in covid 19 induced ards a secondary analysis of the confident trial |
| topic | COVID-19 Convalescent plasma ARDS Immune response Phenotypes |
| url | https://doi.org/10.1186/s13613-024-01392-1 |
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