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Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.
Bergamaschi, Laura; Mescia, Federica; Turner, Lorinda; Hanson, Aimee L; Kotagiri, Prasanti; Dunmore, Benjamin J; Ruffieux, Hélène; De Sa, Aloka; Huhn, Oisín; Morgan, Michael D; Gerber, Pehuén Pereyra; Wills, Mark R; Baker, Stephen; Calero-Nieto, Fernando J; Doffinger, Rainer; Dougan, Gordon; Elmer, Anne; Goodfellow, Ian G; Gupta, Ravindra K; Hosmillo, Myra; Hunter, Kelvin; Kingston, Nathalie; Lehner, Paul J; Matheson, Nicholas J; Nicholson, Jeremy K; Petrunkina, Anna M; Richardson, Sylvia; Saunders, Caroline; Thaventhiran, James E D; Toonen, Erik J M; Weekes, Michael P; Göttgens, Berthold; Toshner, Mark; Hess, Christoph; Bradley, John R; Lyons, Paul A; Smith, Kenneth G C.
  • Bergamaschi L; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Mescia F; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Turner L; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Hanson AL; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Kotagiri P; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Dunmore BJ; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Ruffieux H; MRC Biostatistics Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
  • De Sa A; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Huhn O; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Morgan MD; Cancer Research UK - Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK.
  • Gerber PP; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Wills MR; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Baker S; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Calero-Nieto FJ; Department of Haematology, Wellcome & MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Doffinger R; Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Dougan G; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Elmer A; Cambridge Clinical Research Centre, NIHR Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Goodfellow IG; Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Gupta RK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Hosmillo M; Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Hunter K; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Kingston N; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Lehner PJ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Matheson NJ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; NHS Blood and Transplant, Cambridge, UK.
  • Nicholson JK; The Australian National Phenome Centre, Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, Murdoch, Western Australia WA 6150, Australia.
  • Petrunkina AM; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Richardson S; MRC Biostatistics Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
  • Saunders C; Cambridge Clinical Research Centre, NIHR Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Thaventhiran JED; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; MRC Toxicology Unit, School of Biological Sciences, U
  • Toonen EJM; R&D Department, Hycult Biotech, 5405 PD Uden, the Netherlands.
  • Weekes MP; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
  • Göttgens B; Department of Haematology, Wellcome & MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Toshner M; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Heart and Lung Research Institute, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Royal Papworth Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Hess C; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Department of Biomedicine, University and University
  • Bradley JR; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Lyons PA; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: pal34@cam.ac.uk.
  • Smith KGC; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: kgcs2@cam.ac.uk.
Immunity ; 54(6): 1257-1275.e8, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1230571
ABSTRACT
The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Lymphocyte Activation / CD8-Positive T-Lymphocytes / Host-Pathogen Interactions / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Diagnostic study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.05.010

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Lymphocyte Activation / CD8-Positive T-Lymphocytes / Host-Pathogen Interactions / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Diagnostic study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.05.010