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 Peacock, Sharif A. Ismail*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

71 Citations (Scopus)
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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 languageEnglish
Article number0245532
Number of pages21
JournalPLoS ONE
Issue number1
Publication statusPublished - 25 Jan 2021

Bibliographical note

Funding Information: 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.

Open Access: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher Copyright: © 2021 Shrotri et al.

Citation: Shrotri M, van Schalkwyk MCI, Post N, Eddy D, Huntley C, Leeman D, et al. (2021) T cell response to SARS-CoV-2 infection in humans: A systematic review. PLoS ONE 16(1): e0245532.

DOI: https://doi.org/10.1371/journal.pone.0245532




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