Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Front Immunol. 2024 Oct 28;15:1405013. doi: 10.3389/fimmu.2024.1405013. eCollection 2024.
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.
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.
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.
This study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19.
SARS-CoV-2 大流行对社会造成了广泛而严重的影响，但也有一些患者明显康复的例子，甚至是重症患者。
在这项研究中，我们使用单细胞 RNA 测序来分析中度和重症 COVID-19 患者康复和死亡期间的免疫反应。
扩展的 T 细胞受体（TCR）克隆主要是针对 SARS-CoV-2 的，但在所有患者中仅占总库的一小部分。相比之下，死亡患者表现出无 COVID-19 特异性的单克隆 B 细胞受体（BCR）扩增，而幸存者则表现出多样化和特异性的 BCR 克隆。这些发现表明，TCR 多样性或 BCR 单克隆扩增都不足以清除病毒并随后康复。差异基因表达分析显示，幸存者中富含蛋白质生物合成过程，但死亡患者中潜在的有害线粒体 ATP 代谢被激活。
这项研究强调，BCR 库的多样性，但不是 TCR 多样性，与 COVID-19 的良好结局相关。
