학술논문
Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.
Document Type
Academic Journal
Author
Youngs J; Institute for Infection & Immunity, St. George's University of London, London, United Kingdom.; Clinical Academic Group in Infection and Immunity, St. George's Hospital NHS Trust, London, United Kingdom.; Provine NM; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Lim N; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Sharpe HR; Jenner Institute, University of Oxford, Oxford, United Kingdom.; Amini A; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Chen YL; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.; Luo J; Respiratory Medicine Unit, and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Edmans MD; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Zacharopoulou P; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Chen W; Respiratory Medicine Unit, and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Sampson O; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Paton R; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Hurt WJ; Institute for Infection & Immunity, St. George's University of London, London, United Kingdom.; Clinical Academic Group in Infection and Immunity, St. George's Hospital NHS Trust, London, United Kingdom.; Duncan DA; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.; Diamond Light Source, Harwell Science and Innovation Campus, Didcot, United Kingdom.; McNaughton AL; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Miao VN; Institute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.; Leaver S; Intensive Care Medicine, St George's University Hospital NHS Foundation Trust, London, United Kingdom.; Wyncoll DLA; Intensive Care Medicine, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom.; Ball J; Intensive Care Medicine, St George's University Hospital NHS Foundation Trust, London, United Kingdom.; Hopkins P; Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences, & Medicine, King's College, London, United Kingdom.; Skelly DT; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Barnes E; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Jenner Institute, University of Oxford, Oxford, United Kingdom.; Dunachie S; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Ogg G; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.; Lambe T; Jenner Institute, University of Oxford, Oxford, United Kingdom.; Pavord I; Respiratory Medicine Unit, and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Shalek AK; Institute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.; Thompson CP; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Xue L; Respiratory Medicine Unit, and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Macallan DC; Institute for Infection & Immunity, St. George's University of London, London, United Kingdom.; Clinical Academic Group in Infection and Immunity, St. George's Hospital NHS Trust, London, United Kingdom.; Goulder P; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Klenerman P; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Bicanic T; Institute for Infection & Immunity, St. George's University of London, London, United Kingdom.; Clinical Academic Group in Infection and Immunity, St. George's Hospital NHS Trust, London, United Kingdom.
Source
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
Subject
Language
English
Abstract
Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:WH reports lecture fees from Gilead.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:WH reports lecture fees from Gilead.