Journal
NATURE IMMUNOLOGY
Volume 21, Issue 11, Pages 1336-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-0782-6
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Categories
Funding
- Oxford Immunology Network COVID-19 Response T Cell Consortium (Supplementary Table 4)
- UK Medical Research Council
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China [2018-I2M-2-002]
- National Institutes of Health, National Key R&D Program of China [2020YFE0202400]
- China Scholarship Council
- National Institute for Health Research (NIHR) [CO-CIN-01]
- Medical Research Council [MC_PC_19059]
- Wellcome Trust
- Department for International Development [215091/Z/18/Z]
- Bill and Melinda Gates Foundation [OPP1209135]
- NIHR Oxford Biomedical Research Centre
- Health Protection Research Unit in Respiratory Infections [NIHR200927/WHRG_P82523]
- NIHR Senior Investigator Award [NIHR201385/WHRR P84026]
- Imperial College Biomedical Research Centre [IS-BRC-1215-20013]
- National Institute of Allergy and Infectious Diseases (Consortium for HIV/AIDS Vaccine Development) [UM1 AI 144371, R01 AI 118549]
- NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at the University of Liverpool [NIHR200907]
- Public Health England (PHE)
- Schmidt Futures
- Liverpool School of Tropical Medicine
- University of Oxford
- Wellcome Trust [205228/Z/16/Z, 110058/Z/15/Z, 206377, 095541/A/11/Z]
- MRC [MR/N00065X/1, MC_UU_00008/5, MC_PC_19025, MC_U137881017, MC_PC_19059, MC_UU_00008/6, MC_UU_12010/5, G116/150, MR/L018942/1, MC_PC_20002] Funding Source: UKRI
- UKRI [MR/S032304/1] Funding Source: UKRI
- Wellcome Trust [110058/Z/15/Z] Funding Source: Wellcome Trust
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The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-gamma-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4(+)and/or CD8(+)epitopes, including six immunodominant regions. Six optimized CD8(+)epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8(+)T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design. Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4(+)and CD8(+)T cells that recognize multiple epitopes that span the viral proteome. CD4(+)T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8(+)T cells were found in patients with mild disease.
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