Cellular immune response to SARS-CoV-2 infection in humans: a systematic review

Madhumita Shrotri ORCID logo ; May CI van Schalkwyk ORCID logo ; Nathan Post ; Danielle Eddy ORCID logo ; Catherine Huntley ; David Leeman ORCID logo ; Samuel Rigby ORCID logo ; Sarah V Williams ; William H Bermingham ORCID logo ; Paul Kellam ORCID logo ; +5 more... John Maher ORCID logo ; Adrian M Shields ORCID logo ; Gayatri Amirthalingam ORCID logo ; Sharon J Peacock ORCID logo ; Sharif A Ismail ORCID logo ; (2020) Cellular immune response to SARS-CoV-2 infection in humans: a systematic review. medRxiv preprint - BMJ Yale. ISSN 1468-5833 DOI: 10.1101/2020.08.24.20180679
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ABSTRACT

Introduction

Understanding the cellular immune response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published in recent months.

Methods

For this systematic review, independent keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer for studies published from 01/01/2020-26/06/2020. 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. Almost all studies used observational designs, were hospital-based, 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.

Interpretation

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. In contrast to antibody responses, population-level surveillance of the cellular response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.

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