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Identification of Distinct Immunophenotypes in Critically Ill Coronavirus Disease 2019 Patients.
Dupont, Thibault; Caillat-Zucman, Sophie; Fremeaux-Bacchi, Véronique; Morin, Florence; Lengliné, Etienne; Darmon, Michael; Peffault de Latour, Régis; Zafrani, Lara; Azoulay, Elie; Dumas, Guillaume.
  • Dupont T; Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Caillat-Zucman S; Immunology Laboratory, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Fremeaux-Bacchi V; Immunology Laboratory, European Hospital Georges Pompidou (HEGP), Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Morin F; Immunology Laboratory, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Lengliné E; Hematology Department, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Darmon M; Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Peffault de Latour R; Bone Marrow Transplantation (BMT) Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Zafrani L; Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Azoulay E; Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France.
  • Dumas G; Medical Intensive Care Unit, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France. Electronic address: guillaume.dumas@aphp.fr.
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 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-1ß, 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.
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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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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