T-cell receptor repertoires as potential diagnostic markers for patients with COVID-19

https://doi.org/10.1016/j.ijid.2021.10.033Get rights and content
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Highlights

  • Decreased TCR repertoire diversity and longer CDR3 length were found in COVID-19 patients.

  • TRBV/J gene usage and overlap indices are abnormal in COVID-19 patients.

  • CDR3 length and recombination events are abnormal in COVID-19 patients.

  • Disease-associated TCRβ clones are useful in the diagnosis of COVID-19.

Abstract

Objective

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health emergency. T-cell receptors (TCRs) are crucial mediators of antiviral adaptive immunity. This study sought to comprehensively characterize the TCR repertoire changes in patients with COVID-19.

Methods

A large sample size multi-center randomized controlled trial was implemented to study the features of the TCR repertoire and identify COVID-19 disease-related TCR sequences.

Results

It was found that some T-cell receptor beta chain (TCRβ) features differed markedly between COVID-19 patients and healthy controls, including decreased repertoire diversity, longer complementarity-determining region 3 (CDR3) length, skewed utilization of the TCRβ variable gene/joining gene (TRBV/J), and a high degree of TCRβ sharing in COVID-19 patients. Moreover, this analysis showed that TCR repertoire diversity declines with aging, which may be a cause of the higher infection and mortality rates in elderly patients. Importantly, a set of TCRβ clones that can distinguish COVID-19 patients from healthy controls with high accuracy was identified. Notably, this diagnostic model demonstrates 100% specificity and 82.68% sensitivity at 0–3 days post diagnosis.

Conclusions

This study lays the foundation for immunodiagnosis and the development of medicines and vaccines for COVID-19 patients.

KEYWORDS

Coronavirus disease 2019
T-cell receptor
SARS-CoV-2
Adaptive immunity

Abbreviations

COVID-19
coronavirus disease 2019
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
CDR3
complementarity-determining region 3
TCR
T-cell receptor
TCRβ
T-cell receptor beta chain
TRBV
TCR beta chain variable gene
TRBJ
TCR beta chain joining gene
HC
Healthy control
DLS
Discovery Life Science
BWNW
Bloodworks Northwest
HUniv12Oct
Hospital Univesitario 12 de Octubre

Cited by (0)

1

Xianliang Hou, Wentao Fan, and Guangyu Wang contributed equally to this work.