AUTHOR=Paran Faith Jessica , Oyama Rieko , Khasawneh Abdullah , Ai Tomohiko , Ismanto Hendra Saputra , Sherif Aalaa Alrahman , Saputri Dianita Susilo , Ono Chikako , Saita Mizue , Takei Satomi , Horiuchi Yuki , Yagi Ken , Matsuura Yoshiharu , Okazaki Yasushi , Takahashi Kazuhisa , Standley Daron M. , Tabe Yoko , Naito Toshio TITLE=BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1405013 DOI=10.3389/fimmu.2024.1405013 ISSN=1664-3224 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.