1. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia
- Author
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Mirjam Lutz, Ekaterina Friebel, Roland S. Liblau, Antoine Roquilly, Guillaume Martin-Blondel, Manfred Claassen, Benjamin Gaborit, Manuel Kauffmann, Sepideh Babaei, Donatella De Feo, Nicolás Gonzalo Núñez, Nisar P. Malek, Chiara Alberti, Sally Al-Hajj, Susanne Unger, Siri Goepel, Ikram Ayoub, Helene A. Häberle, Jakob Nilsson, Nicole Puertas Jurado, Peter Rosenberger, Stefanie Kreutmair, Sinduya Krishnarajah, Burkhard Becher, Michael Bitzer, Florian Ingelfinger, Pistre, Karine, Universität Zürich [Zürich] = University of Zurich (UZH), German Cancer Consortium [Heidelberg] (DKTK), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institute of Experimental Immunology [Zurich], Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University hospital of Zurich [Zurich], University of Zurich, and Becher, Burkhard
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,MESH: CD4-Positive T-Lymphocytes / immunology ,MESH: Biomarkers / blood ,[SDV]Life Sciences [q-bio] ,MESH: HLA Antigens / genetics ,MESH: COVID-19 / pathology ,10263 Institute of Experimental Immunology ,Hospital-acquired pneumonia ,Severity of Illness Index ,0302 clinical medicine ,MESH: Pneumonia / immunology ,HLA Antigens ,T-Lymphocyte Subsets ,peptide binding strength ,Immunopathology ,Immunology and Allergy ,MESH: Pneumonia / pathology ,MESH: T-Lymphocyte Subsets / metabolism ,COVID ,high-dimensional single cell analysis ,Antigen Presentation ,MESH: Middle Aged ,spectral flow cytometry ,immune profiling ,MESH: SARS-CoV-2 / immunology ,Middle Aged ,Acquired immune system ,MESH: HLA Antigens / immunology ,3. Good health ,[SDV] Life Sciences [q-bio] ,Infectious Diseases ,HLA typing ,030220 oncology & carcinogenesis ,MESH: T-Lymphocyte Subsets / immunology ,2723 Immunology and Allergy ,MESH: SARS-CoV-2 / pathogenicity ,Biomarker (medicine) ,Cytokines ,biomarker ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,MESH: Immunity, Innate ,Angiotensin-Converting Enzyme 2 ,Adult ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Immunophenotyping ,Immunology ,Antigen presentation ,610 Medicine & health ,Human leukocyte antigen ,Biology ,Article ,03 medical and health sciences ,MESH: Natural Killer T-Cells / immunology ,Immune system ,immunophenotyping ,MESH: CD4-Positive T-Lymphocytes / metabolism ,MESH: Angiotensin-Converting Enzyme 2 / metabolism ,MESH: Severity of Illness Index ,medicine ,Humans ,2403 Immunology ,SARS-CoV-2 ,COVID-19 ,GM-CSF ,2725 Infectious Diseases ,Pneumonia ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,MESH: COVID-19 / immunology ,Immunity, Innate ,030104 developmental biology ,MESH: Antigen Presentation ,10033 Clinic for Immunology ,570 Life sciences ,biology ,Natural Killer T-Cells ,Biomarkers - Abstract
Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2-petides to the patients’ HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Towards clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19., Graphical Abstract, The pathogen-specific immune alterations in severe COVID-19 remain unknown. Using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided comparison of COVID-19 vs. non-SARS-CoV-2-pneumonia patient samples, Kreutmair et al. identify T and NK cell immune signatures specific to SARS-CoV-2. They furthermore reveal NKT cell frequency as a predictive biomarker for COVID-19 outcome prediction and link impaired virus recognition to HLA genetics.
- Published
- 2021
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