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T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
Ogbe, Ane; Kronsteiner, Barbara; Skelly, Donal T; Pace, Matthew; Brown, Anthony; Adland, Emily; Adair, Kareena; Akhter, Hossain Delowar; Ali, Mohammad; Ali, Serat-E; Angyal, Adrienn; Ansari, M Azim; Arancibia-Cárcamo, Carolina V; Brown, Helen; Chinnakannan, Senthil; Conlon, Christopher; de Lara, Catherine; de Silva, Thushan; Dold, Christina; Dong, Tao; Donnison, Timothy; Eyre, David; Flaxman, Amy; Fletcher, Helen; Gardner, Joshua; Grist, James T; Hackstein, Carl-Philipp; Jaruthamsophon, Kanoot; Jeffery, Katie; Lambe, Teresa; Lee, Lian; Li, Wenqin; Lim, Nicholas; Matthews, Philippa C; Mentzer, Alexander J; Moore, Shona C; Naisbitt, Dean J; Ogese, Monday; Ogg, Graham; Openshaw, Peter; Pirmohamed, Munir; Pollard, Andrew J; Ramamurthy, Narayan; Rongkard, Patpong; Rowland-Jones, Sarah; Sampson, Oliver; Screaton, Gavin; Sette, Alessandro; Stafford, Lizzie; Thompson, Craig.
  • Ogbe A; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Kronsteiner B; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Skelly DT; Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
  • Pace M; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Brown A; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Adland E; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
  • Adair K; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Akhter HD; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Ali M; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Ali SE; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
  • Angyal A; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Ansari MA; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Arancibia-Cárcamo CV; Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
  • Brown H; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
  • Chinnakannan S; The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.
  • Conlon C; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • de Lara C; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
  • de Silva T; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
  • Dold C; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Dong T; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Donnison T; Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
  • Eyre D; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Flaxman A; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Fletcher H; The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.
  • Gardner J; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Grist JT; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Hackstein CP; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Jaruthamsophon K; Chinese Academy of Medical Science Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Jeffery K; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Lambe T; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Lee L; Big Data Institute, Nuffield Department. of Population Health, University of Oxford, Oxford, UK.
  • Li W; Jenner Institute, University of Oxford, Oxford, UK.
  • Lim N; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
  • Matthews PC; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
  • Mentzer AJ; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Moore SC; Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
  • Naisbitt DJ; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
  • Ogese M; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Ogg G; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
  • Openshaw P; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Pirmohamed M; Jenner Institute, University of Oxford, Oxford, UK.
  • Pollard AJ; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Ramamurthy N; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Rongkard P; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Rowland-Jones S; Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
  • Sampson O; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Screaton G; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Sette A; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Stafford L; HPRU in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Thompson C; Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Nat Commun ; 12(1): 2055, 2021 04 06.
Article in English | MEDLINE | ID: covidwho-1171493
Semantic information from SemMedBD (by NLM)
1. Antigens PART_OF Voluntary Workers
Subject
Antigens
Predicate
PART_OF
Object
Voluntary Workers
2. Immune response PROCESS_OF Exposed Population
Subject
Immune response
Predicate
PROCESS_OF
Object
Exposed Population
3. Antigens PART_OF Voluntary Workers
Subject
Antigens
Predicate
PART_OF
Object
Voluntary Workers
4. Immune response PROCESS_OF Exposed Population
Subject
Immune response
Predicate
PROCESS_OF
Object
Exposed Population
ABSTRACT
Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Immunoassay / T-Lymphocytes / Cross Reactions / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21856-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Immunoassay / T-Lymphocytes / Cross Reactions / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21856-3