ArticleNature communications2021
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
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In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
8.3field-weighted citation impact, top 2% of its field
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Pooled it
- Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.JCI insight · 2022Trial
- Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial.The Journal of clinical investigation · 2021Trial
- Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial.The lancet. HIV · 2021Trial
- Predictive markers of SARS-CoV-2 spike-specific cytotoxic T cell activity following Omicron breakthrough infection.Emerging microbes & infections · 2026Article
- Mechanisms underlying immunodynamics of layered defenses elicited by mRNA vaccination in children.BMC medicine · 2026Article
- Pre-COVID-19 ex vivo cross-reactive IFN-γ cellular response to SARS-CoV-2 spike overlapping peptides is more prevalent among Kenyan compared to Swedish adults.BMC infectious diseases · 2026Article
- Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity.Scientific reports · 2025Observational
- Whole-Blood Cellular Responses: A Promising Indicator of SARS-CoV-2 Immunity Compared to Serology.Journal of clinical medicine · 2025Article
- Dosing interval is a major factor determining the quality of T cells induced by SARS-CoV-2 mRNA and adenoviral vector vaccines.Science immunology · 2025Article
- Compartmentalised mucosal and blood immunity to SARS-CoV-2 is associated with high seroprevalence before the Delta wave in Africa.Communications medicine · 2025Article
- A systems biology approach to define SARS-CoV-2 correlates of protection.NPJ vaccines · 2025Article
- Enhanced and long-lasting SARS-CoV-2 immune memory in individuals with common cold coronavirus cross-reactive T cell immunity.Frontiers in immunology · 2025Article
- Heterologous prime-pull mucosal vaccination with an adjuvanted RBD vaccine elicits robust IgA production and protects against SARS-CoV-2.Frontiers in immunology · 2025Article
- T-Cell Interferon Gamma Responses to SARS-CoV-2 Following Infection with/Without Vaccination in a Tanzanian Population.Infection and drug resistance · 2025Article
- COVID-19 vaccinated children, adolescents, and young adults with acute lymphoblastic leukemia show spike reactive antibodies and multifunctional T-cells.International journal of cancer · 2024Article
- Obesity differs from diabetes mellitus in antibody and T-cell responses post-COVID-19 recovery.Clinical and experimental immunology · 2024Article
- Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.Nature protocols · 2024Review
- Cytokine profile of anti-spike CD4iScience · 2024Article
- Lack of memory recall in human CD4 T cells elicited by the first encounter with SARS-CoV-2.iScience · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
63 authors at 8 institutions in 3 countries.
Ane Ogbe *Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0001-7774-7215
Barbara Kronsteiner *Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Donal T Skelly *Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0002-2426-3097
Matthew Pace *Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Anthony Brown *Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0001-6751-3300
Emily Adland *Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Kareena AdairDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Hossain Delowar AkhterNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Mohammad AliNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0003-0170-7182
Serat-E AliDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Adrienn AngyalThe Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.
M Azim AnsariNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Carolina V Arancibia-CárcamoNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Helen BrownNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Senthil ChinnakannanNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0002-4404-0229
Christopher ConlonNuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.ORCID 0000-0002-3531-2464
Catherine de LaraNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Thushan de SilvaThe Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.
Christina DoldOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Tao DongMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Timothy DonnisonNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0001-6568-7761
David EyreOxford University Hospitals NHS Foundation Trust, Oxford, UK.
Amy FlaxmanJenner Institute, University of Oxford, Oxford, UK.ORCID 0000-0001-6460-1372
Helen FletcherDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.ORCID 0000-0002-0435-1006
Joshua GardnerDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
James T GristNIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Carl-Philipp HacksteinNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Kanoot JaruthamsophonDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.ORCID 0000-0003-1563-0024
Katie JefferyOxford University Hospitals NHS Foundation Trust, Oxford, UK.ORCID 0000-0002-6506-2689
Teresa LambeJenner Institute, University of Oxford, Oxford, UK.ORCID 0000-0001-7711-897X
Lian LeeNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0003-3915-3015
Wenqin LiNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Nicholas LimNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Philippa C MatthewsNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0002-4036-4269
Alexander J MentzerOxford University Hospitals NHS Foundation Trust, Oxford, UK.ORCID 0000-0002-4502-2209
Shona C MooreHPRU in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.ORCID 0000-0001-8610-2806
Dean J NaisbittDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Monday OgeseDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Graham OggOxford University Hospitals NHS Foundation Trust, Oxford, UK.
Peter OpenshawFaculty of Medicine, National Heart and Lung institute, Imperial College, London, UK.ORCID 0000-0002-7220-2555
Munir PirmohamedDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Andrew J PollardOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.ORCID 0000-0001-7361-719X
Narayan RamamurthyNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Patpong RongkardNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Sarah Rowland-JonesThe Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.
Oliver SampsonNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0001-8727-0588
Gavin ScreatonWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Alessandro SetteCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.
Lizzie StaffordOxford University Hospitals NHS Foundation Trust, Oxford, UK.
Craig ThompsonPeter Medawar Building for Pathogen Research, Department of Zoology, University of Oxford, Oxford, UK.ORCID 0000-0001-9248-9365
Paul J ThomsonDepartment of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Ryan ThwaitesFaculty of Medicine, National Heart and Lung institute, Imperial College, London, UK.ORCID 0000-0003-3052-2793
Vinicius VieiraNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0002-4901-0424
Daniela WeiskopfCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.
Panagiota ZacharopoulouNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Oxford Immunology Network Covid-19 Response T Cell Consortium
Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team
Lance TurtleHPRU in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.ORCID 0000-0002-0778-1693
Paul KlenermanNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK. paul.klenerman@ndm.ox.ac.uk.ORCID 0000-0003-4307-9161
Philip GoulderPeter Medawar Building for Pathogen Research, Department of Paediatrics, University of Oxford, Oxford, UK.
John FraterNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0001-7163-7277
Eleanor BarnesNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0002-0860-0831
Susanna DunachieNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.ORCID 0000-0001-5665-6293
University of Oxford · GBUniversity of Liverpool · GBOxford University Hospitals NHS Trust · GBCentre for Human Genetics · GBImperial College London · GBLos Angeles County Department of Public Health · USUniversity of Sheffield · GBLondon School of Hygiene & Tropical Medicine · GB
Funding
Department of Health NIHR200907Medical Research Council MC_PC_19059Medical Research Council MC_PC_20002Medical Research Council MC_UU_00008/5Medical Research Council MR/L006588/1Medical Research Council MR/L006758/1Medical Research Council MR/L018942/1Medical Research Council MR/P011233/1Medical Research Council MR/V028448/1Wellcome Trust 108869/Z/15/ZWellcome Trust 109965/Z/15/ZWellcome Trust 110110/Z/15/ZWellcome Trust 205228/Z/16/ZWellcome Trust 220171/Z/20/ZWellcome Trust WT109965MA
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.
Indexed as
Antiviral AgentsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCOVID-19Cross ReactionsCytokinesHealth PersonnelHEK293 CellsHumansImmunoassayImmunoglobulin GImmunologic MemoryInterferon-gammaPandemicsPeptidesAntiviral AgentsCytokinesImmunoglobulin GInterferon-gammaPeptides
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