BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis

Front Immunol. 2024 Oct 28:15:1405013. doi: 10.3389/fimmu.2024.1405013. eCollection 2024.

Abstract

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients.

Materials and methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages.

Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased.

Conclusion: This study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19.

Keywords: COVID - 19; gene expression; immune repertoire analysis; immunology & infectious diseases; single cell RNA and transcriptome sequencing.

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology
  • COVID-19* / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Antigen, B-Cell* / genetics
  • Receptors, Antigen, B-Cell* / immunology
  • Receptors, Antigen, B-Cell* / metabolism
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • SARS-CoV-2* / immunology
  • Single-Cell Analysis

Substances

  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was partially supported by the Japan Agency for Medical Research and Development (JP20fk0108472 to TN), by Japan Society for the Promotion of Science Grants-in Aid for Scientific Research (22K08608 to MS and 22K15675 to ST) and by Research Support Project for Life Science and Drug Discovery (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED (JP22ama121025 to DS).