Identification of Distinct Immunophenotypes in Critically Ill Coronavirus Disease 2019 Patients.
Chest
; 159(5): 1884-1893, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1028464
ABSTRACT
BACKGROUND:
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 coronavirus disease 2019 (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 ANDMETHODS:
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 with 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-1ß, IL-8, tumor necrosis factor-alpha [TNFâº]) associated with CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).INTERPRETATION:
Patients with severe COVID-19 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Biomarkers
/
Common Variable Immunodeficiency
/
Complement Activation
/
COVID-19
/
Inflammation
Type of study:
Cohort study
/
Diagnostic study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Long Covid
Limits:
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
English
Journal:
Chest
Year:
2021
Document Type:
Article
Affiliation country:
J.chest.2020.11.049
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