Madhumita Shrotri1,2, May C I van Schalkwyk3, Nathan Post1, Danielle Eddy2, Catherine Huntley1, David Leeman2, Samuel Rigby1, Sarah V Williams1, William H Bermingham4, Paul Kellam5, John Maher6,7, Adrian M Shields8, Gayatri Amirthalingam2, Sharon J Peacock2,9, Sharif A Ismail2,10,11. 1. Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom. 2. National Infection Service, Public Health England, London, United Kingdom. 3. Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, United Kingdom. 4. Department of Clinical Immunology, University Hospitals Birmingham, Birmingham, United Kingdom. 5. Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom. 6. School of Cancer and Pharmaceutical Studies, King's College London, London, United Kingdom. 7. Department of Immunology, Eastbourne Hospital, Eastbourne, United Kingdom. 8. Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom. 9. Department of Medicine, University of Cambridge, Cambridge, United Kingdom. 10. Department of Primary Care and Public Health, Imperial College London, London, United Kingdom. 11. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Abstract
BACKGROUND: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. METHODS: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. CONCLUSION: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.
BACKGROUND: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. METHODS: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. CONCLUSION: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.
Authors: Nathan Post; Danielle Eddy; Catherine Huntley; May C I van Schalkwyk; Madhumita Shrotri; David Leeman; Samuel Rigby; Sarah V Williams; William H Bermingham; Paul Kellam; John Maher; Adrian M Shields; Gayatri Amirthalingam; Sharon J Peacock; Sharif A Ismail Journal: PLoS One Date: 2020-12-31 Impact factor: 3.240
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