Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial

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

Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial

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 MoutschenPierre-François Laterre

Research output: Contribution to journal › Article › peer-review

9 Downloads (Pure)

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 .

Original language	English
Article number	160
Number of pages	11
Journal	Annals of Intensive Care
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/s13613-024-01392-1
Publication status	Published - Dec 2024

Bibliographical note

Funding Information:
The CONFIDENT trial was funded by a Belgian federal grant KCE 2020 and the cluster substudy by grants \u201C1-0-1 AXA\u201D 2021 and Li\u00E8ge University 2021.

Publisher Copyright:
© The Author(s) 2024.

Access to Document

10.1186/s13613-024-01392-1Licence: CC BY

120902105Final published version, 1.23 MBLicence: CC BY

Handle.net

Persistent link

Cite this

Misset, B., Diep, A. N., Bertrand, A., Piagnerelli, M., Hoste, E., Michaux, I., De Waele, E., Dumoulin, A., Jorens, P. G., van der Hauwaert, E., Vallot, F., Swinnen, W., De Schryver, N., de Mey, N., Layios, N., Mesland, J.-B., Robinet, S., Cavalier, E., Donneau, A.-F., ... Laterre, P.-F. (2024). Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial. Annals of Intensive Care, 14(1), Article 160. https://doi.org/10.1186/s13613-024-01392-1

@article{b49265575bca41b3ace4fa2c4c627e58,

title = "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, 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 Li{\`e}ge CE 2020/239.CLINICALTRIALS: gov NCT04558476. Registered 2020-09-11, https://www.CLINICALTRIALS: gov/study/NCT04558476 .",

author = "Beno{\^i}t Misset and Diep, {Anh Nguyet} and Axelle Bertrand and Michael Piagnerelli and Eric Hoste and Isabelle Michaux and {De Waele}, Elisabeth and Alexander Dumoulin and Jorens, {Philippe G} and {van der Hauwaert}, Emmanuel and Fr{\'e}d{\'e}ric Vallot and Walter Swinnen and {De Schryver}, Nicolas and {de Mey}, Nathalie and Nathalie Layios and Jean-Baptiste Mesland and S{\'e}bastien Robinet and Etienne Cavalier and Anne-Fran{\c c}oise Donneau and Michel Moutschen and Pierre-Fran{\c c}ois Laterre",

note = "Funding Information: The CONFIDENT trial was funded by a Belgian federal grant KCE 2020 and the cluster substudy by grants \u201C1-0-1 AXA\u201D 2021 and Li\u00E8ge University 2021. Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1186/s13613-024-01392-1",

language = "English",

volume = "14",

journal = "Annals of Intensive Care",

issn = "2110-5820",

publisher = "Springer-Verlag GmbH and Co. KG",

number = "1",

}

Misset, B, Diep, AN, Bertrand, A, Piagnerelli, M, Hoste, E, Michaux, I, De Waele, E, Dumoulin, A, Jorens, PG, van der Hauwaert, E, Vallot, F, Swinnen, W, De Schryver, N, de Mey, N, Layios, N, Mesland, J-B, Robinet, S, Cavalier, E, Donneau, A-F, Moutschen, M & Laterre, P-F 2024, 'Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial', Annals of Intensive Care, vol. 14, no. 1, 160. https://doi.org/10.1186/s13613-024-01392-1

TY - JOUR

T1 - Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS

T2 - a secondary analysis of the CONFIDENT trial

AU - Misset, Benoît

AU - Diep, Anh Nguyet

AU - Bertrand, Axelle

AU - Piagnerelli, Michael

AU - Hoste, Eric

AU - Michaux, Isabelle

AU - De Waele, Elisabeth

AU - Dumoulin, Alexander

AU - Jorens, Philippe G

AU - van der Hauwaert, Emmanuel

AU - Vallot, Frédéric

AU - Swinnen, Walter

AU - De Schryver, Nicolas

AU - de Mey, Nathalie

AU - Layios, Nathalie

AU - Mesland, Jean-Baptiste

AU - Robinet, Sébastien

AU - Cavalier, Etienne

AU - Donneau, Anne-Françoise

AU - Moutschen, Michel

AU - Laterre, Pierre-François

N1 - Funding Information: The CONFIDENT trial was funded by a Belgian federal grant KCE 2020 and the cluster substudy by grants \u201C1-0-1 AXA\u201D 2021 and Li\u00E8ge University 2021. Publisher Copyright: © The Author(s) 2024.

PY - 2024/12

Y1 - 2024/12

N2 - 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 .

AB - 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 .

UR - http://www.scopus.com/inward/record.url?scp=85207032731&partnerID=8YFLogxK

U2 - 10.1186/s13613-024-01392-1

DO - 10.1186/s13613-024-01392-1

M3 - Article

C2 - 39432177

SN - 2110-5820

VL - 14

JO - Annals of Intensive Care

JF - Annals of Intensive Care

IS - 1

M1 - 160

ER -

Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial

Abstract

Bibliographical note

Access to Document

Handle.net

Other files and links

Fingerprint

Cite this