tetano
Editor, Senior Moderator
Chest
. 2020 Dec 11;S0012-3692(20)35351-4.
doi: 10.1016/j.chest.2020.11.049. Online ahead of print.
Identification of distinct immunophenotypes in critically-ill COVID-19 patients
Thibault Dupont[SUP] 1 [/SUP], Sophie Caillat-Zucman[SUP] 2 [/SUP], V?ronique Fremeaux-Bacchi[SUP] 3 [/SUP], Florence Morin[SUP] 2 [/SUP], Etienne Lenglin?[SUP] 4 [/SUP], Michael Darmon[SUP] 1 [/SUP], R?gis Peffault de Latour[SUP] 5 [/SUP], Lara Zafrani[SUP] 1 [/SUP], Elie Azoulay[SUP] 1 [/SUP], Guillaume Dumas[SUP] 6 [/SUP]
Affiliations
Abstract
Bsackground: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation and inflammatory reaction leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically-ill COVID-19 patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients.
Research question: Are critically-ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?
Study design and methods: We did a single-center, prospective study in an ICU department in France. Ninety-six critically-ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission.
Results: We found that patients were distributed in three clusters bearing distinct immunologic features and associated to different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, TNF⍺) associated to CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).
Interpretation: Severe COVID-19 patients exhibiting cytokine release marks, complement activation or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility.
. 2020 Dec 11;S0012-3692(20)35351-4.
doi: 10.1016/j.chest.2020.11.049. Online ahead of print.
Identification of distinct immunophenotypes in critically-ill COVID-19 patients
Thibault Dupont[SUP] 1 [/SUP], Sophie Caillat-Zucman[SUP] 2 [/SUP], V?ronique Fremeaux-Bacchi[SUP] 3 [/SUP], Florence Morin[SUP] 2 [/SUP], Etienne Lenglin?[SUP] 4 [/SUP], Michael Darmon[SUP] 1 [/SUP], R?gis Peffault de Latour[SUP] 5 [/SUP], Lara Zafrani[SUP] 1 [/SUP], Elie Azoulay[SUP] 1 [/SUP], Guillaume Dumas[SUP] 6 [/SUP]
Affiliations
- PMID: 33316234
- DOI: 10.1016/j.chest.2020.11.049
Abstract
Bsackground: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation and inflammatory reaction leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically-ill COVID-19 patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients.
Research question: Are critically-ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?
Study design and methods: We did a single-center, prospective study in an ICU department in France. Ninety-six critically-ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission.
Results: We found that patients were distributed in three clusters bearing distinct immunologic features and associated to different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, TNF⍺) associated to CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).
Interpretation: Severe COVID-19 patients exhibiting cytokine release marks, complement activation or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility.