T cell receptor β repertoires in patients with COVID-19 reveal disease severity signatures

Front Immunol. 2023 Jul 5:14:1190844. doi: 10.3389/fimmu.2023.1190844. eCollection 2023.

Abstract

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity.

Methods: In this study, we employed high-throughput T cell receptor (TCR) β repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes.

Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression.

Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR β repertoires in monitoring disease development and indicating disease severity.

Keywords: T cell receptor β repertoire; T cells; coronavirus disease 2019; immunology; machine learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • Patient Acuity
  • Receptors, Antigen, T-Cell / genetics
  • SARS-CoV-2
  • T-Lymphocytes

Substances

  • Receptors, Antigen, T-Cell

Grants and funding

This work was supported by the Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1–009); the National Natural Science Foundation of China (No.32000460). FL was supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB38010400, XDC01000000), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), National Natural Science Foundation of China (NSFC) (81930056), Science and Technology Service Network Initiative of Chinese Academy of Sciences (KFJ-STS-QYZD-2021-08-001, KFJ-STS-ZDTP-079), and Naif Arab University for Security Sciences (NAUSS-23-R18, NAUSS-23-R19).