Table2_BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis.xlsx

IntroductionThe 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 methodsIn 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.
ResultsExpanded 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.
ConclusionThis study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19.

引言
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发的大流行对全球社会造成了广泛且严重的冲击，但即便在重症患者中，也存在诸多实现显著康复的案例。

材料与方法
本研究采用单细胞RNA测序（single-cell RNA sequencing）技术，对中度及重症阶段的康复与死亡新型冠状病毒肺炎（COVID-19）患者的免疫应答进行分析。

结果
扩增的T细胞受体（T cell receptor, TCR）克隆主要为SARS-CoV-2特异性克隆，但在所有受试患者的总TCR库中仅占极小比例。与之形成对照的是，死亡患者呈现出无COVID-19病毒特异性的单克隆B细胞受体（B cell receptor, BCR）扩增，而存活患者则表现出多样化且具有病毒特异性的BCR克隆。上述研究结果表明，无论是T细胞受体多样性还是B细胞单克隆扩增，均不足以实现病毒清除与后续康复。差异基因表达分析显示，存活患者体内富集了蛋白质生物合成相关生物学过程，而死亡患者则激活了具有潜在损伤性的线粒体ATP代谢通路。

结论
本研究强调，B细胞受体库多样性而非T细胞受体多样性，与COVID-19患者的良好预后存在显著相关性。