T cell response to SARS-CoV-2 infection in humans: A systematic review

Madhumita Shrotri; May C. I. Van Schalkwyk; Nathan Post; Danielle Eddy; Catherine Huntley; 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

doi:10.1371/journal.pone.0245532

T cell response to SARS-CoV-2 infection in humans: A systematic review

Madhumita Shrotri, May C. I. Van Schalkwyk, Nathan Post, Danielle Eddy, Catherine Huntley, 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	e0245532
Number of pages	21
Journal	PLOS One
Volume	16
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0245532
Publication status	Published - 25 Jan 2021

Bibliographical note

Funding:
The authors received no specific funding for this work. MCIvS is funded by a NIHR Doctoral Fellowship (Ref NIHR300156). JM acknowledges the support of the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. SAI is supported by a Wellcome Trust Clinical Research Training Fellowship (Ref No 215654/Z/19/Z). The views expressed in this paper are those of the authors only, and do not necessarily represent those of the NHS, the NIHR, PHE or the Department of Health.

Keywords

COVID-19/complications
Host-Pathogen Interactions
Humans
Immunity, Cellular
Lymphopenia/etiology
SARS-CoV-2/immunology
T-Lymphocytes/immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Shrotri, M., Van Schalkwyk, M. C. I., Post, N., Eddy, D., Huntley, C., Leeman, D., Rigby, S., Williams, S. V., Bermingham, W. H., Kellam, P., Maher, J., Shields, A. M., Amirthalingam, G., Peacock, S. J., & Ismail, S. A. (2021). T cell response to SARS-CoV-2 infection in humans: A systematic review. PLOS One, 16(1), Article e0245532. https://doi.org/10.1371/journal.pone.0245532

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title = "T cell response to SARS-CoV-2 infection in humans: A systematic review",

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.",

keywords = "COVID-19/complications, Host-Pathogen Interactions, Humans, Immunity, Cellular, Lymphopenia/etiology, SARS-CoV-2/immunology, T-Lymphocytes/immunology",

author = "Madhumita Shrotri and {Van Schalkwyk}, {May C. I.} and Nathan Post and Danielle Eddy and Catherine Huntley and David Leeman and Samuel Rigby and Williams, {Sarah V.} and Bermingham, {William H.} and Paul Kellam and John Maher and Shields, {Adrian M.} and Gayatri Amirthalingam and Peacock, {Sharon J.} and Ismail, {Sharif A.}",

note = "Funding: The authors received no specific funding for this work. MCIvS is funded by a NIHR Doctoral Fellowship (Ref NIHR300156). JM acknowledges the support of the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. SAI is supported by a Wellcome Trust Clinical Research Training Fellowship (Ref No 215654/Z/19/Z). The views expressed in this paper are those of the authors only, and do not necessarily represent those of the NHS, the NIHR, PHE or the Department of Health. ",

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doi = "10.1371/journal.pone.0245532",

language = "English",

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T2 - A systematic review

AU - Shrotri, Madhumita

AU - Van Schalkwyk, May C. I.

AU - Post, Nathan

AU - Eddy, Danielle

AU - Huntley, Catherine

AU - Leeman, David

AU - Rigby, Samuel

AU - Williams, Sarah V.

AU - Bermingham, William H.

AU - Kellam, Paul

AU - Maher, John

AU - Shields, Adrian M.

AU - Amirthalingam, Gayatri

AU - Peacock, Sharon J.

AU - Ismail, Sharif A.

N1 - Funding: The authors received no specific funding for this work. MCIvS is funded by a NIHR Doctoral Fellowship (Ref NIHR300156). JM acknowledges the support of the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. SAI is supported by a Wellcome Trust Clinical Research Training Fellowship (Ref No 215654/Z/19/Z). The views expressed in this paper are those of the authors only, and do not necessarily represent those of the NHS, the NIHR, PHE or the Department of Health.

PY - 2021/1/25

Y1 - 2021/1/25

N2 - 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.

AB - 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.

KW - COVID-19/complications

KW - Host-Pathogen Interactions

KW - Humans

KW - Immunity, Cellular

KW - Lymphopenia/etiology

KW - SARS-CoV-2/immunology

KW - T-Lymphocytes/immunology

U2 - 10.1371/journal.pone.0245532

DO - 10.1371/journal.pone.0245532

M3 - Article

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SN - 1932-6203

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JO - PLOS One

JF - PLOS One

IS - 1

M1 - e0245532

ER -

T cell response to SARS-CoV-2 infection in humans: A systematic review

Abstract

Bibliographical note

Keywords

UN SDGs

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Cite this