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Published on: December 19, 2020
Identification of Distinct Immunophenotypes in Critically Ill Coronavirus Disease 2019 Patients
Thibault Dupont1, Sophie Caillat-Zucman2, Véronique Fremeaux-Bacchi3
1Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
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 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 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-1β, IL-8, tumor necrosis factor-alpha [TNF⍺]) 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.
Insights
Critically ill COVID-19 patients exhibit distinct immune profiles, including humoral immunodeficiency, hyperinflammation, or complement activation. These immunologic differences suggest personalized therapeutic strategies are needed for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.
Area of Science:
- Immunology
- Virology
- Critical Care Medicine
Background:
- Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes severe lung damage and multi-organ dysfunction.
- Critically ill coronavirus disease 2019 (COVID-19) patients display varied disease trajectories.
- Existing clinical trials explore targeted therapies for the exaggerated inflammatory response in COVID-19.
Purpose of the Study:
- To determine if critically ill COVID-19 patients can be biologically and immunologically classified.
- To investigate patient stratification based on profiles of therapeutic targets.
Main Methods:
- A prospective, single-center study enrolled 96 critically ill adult patients with SARS-CoV-2 infection.
- Principal components analysis and hierarchical clustering were performed on immunological variables.
- Measurements were taken on the day of ICU admission.
Main Results:
- Patients were categorized into three distinct clusters with unique immunological features and ICU outcomes.
- Cluster 1: Humoral immunodeficiency (B-lymphocyte defects, hypogammaglobulinemia).
- Cluster 2: Hyperinflammatory (high cytokines, T-lymphocyte defects).
- Cluster 3: Complement-dependent (terminal complement activation).
Conclusions:
- Severe COVID-19 patients show distinct immunological phenotypes: cytokine release, complement activation, or B-lymphocyte defects.
- This variability supports tailored therapeutic approaches for different patient subgroups.
- Immunological profiling can aid in patient identification and clinical trial eligibility for COVID-19.
