Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, No. 291, Zhongzheng Rd., Zhonghe Dist., New Taipei City, 235, Taiwan.
J Clin Immunol. 2021 Aug;41(6):1131-1145. doi: 10.1007/s10875-021-01045-z. Epub 2021 May 5.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a public health emergency. The most common symptoms of COVID-19 are fever, cough, and fatigue. While most patients with COVID-19 present with mild illness, some patients develop pneumonia, an important risk factor for mortality, at early stage of viral infection, putting these patients at increased risk of death. So far, little has been known about differences in the T cell repertoires between COVID-19 patients with and without pneumonia during SARS-CoV-2 infection. Herein, we aimed to investigate T cell receptor (TCR) repertoire profiles and patient-specific SARS-CoV-2-associated TCR clusters between COVID-19 patients with mild disease (no sign of pneumonia) and pneumonia. The TCR sequencing was conducted to characterize the peripheral TCR repertoire profile and diversity. The TCR clustering and CDR3 annotation were exploited to further discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. Our study indicated a slight decrease in the TCR repertoire diversity and a skewed CDR3 length usage in patients with pneumonia compared to those with mild disease. The SARS-CoV-2-associated TCR clusters enriched in patients with mild disease exhibited significantly higher TCR generation probabilities and most of which were highly shared among patients, compared with those from pneumonia patients. Importantly, using similarity network-based clustering followed by the sequence conservation analysis, we found different patterns of CDR3 sequence motifs between mild disease- and pneumonia-specific SARS-CoV-2-associated public TCR clusters. Our results showed that characteristics of overall TCR repertoire and SARS-CoV-2-associated TCR clusters/clonotypes were divergent between COVID-19 patients with mild disease and patients with pneumonia. These findings provide important insights into the correlation between the TCR repertoire and disease severity in COVID-19 patients.
新型冠状病毒病 2019（COVID-19）大流行是由严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）引起的公共卫生紧急事件。COVID-19 的最常见症状是发烧、咳嗽和疲劳。虽然大多数 COVID-19 患者表现为轻症，但一些患者在病毒感染的早期就会出现肺炎，这是导致死亡的一个重要危险因素，使这些患者的死亡风险增加。到目前为止，对于 COVID-19 患者在 SARS-CoV-2 感染期间有无肺炎的 T 细胞库之间的差异知之甚少。在此，我们旨在研究轻度疾病（无肺炎迹象）和肺炎 COVID-19 患者之间 T 细胞受体（TCR）库谱和患者特异性 SARS-CoV-2 相关 TCR 簇的差异。我们进行了 TCR 测序以描述外周 TCR 库谱和多样性。利用 TCR 聚类和 CDR3 注释进一步发现具有潜在 SARS-CoV-2 抗原特异性的患者特异性 TCR 克隆型的群组。我们的研究表明，与轻度疾病患者相比，肺炎患者的 TCR 库谱多样性略有下降，CDR3 长度使用呈偏斜。与肺炎患者相比，在轻度疾病患者中富集的 SARS-CoV-2 相关 TCR 簇中，TCR 生成概率显著更高，并且大多数 TCR 簇在患者之间高度共享。重要的是，使用基于相似性网络的聚类和序列保守性分析，我们发现轻度疾病和肺炎特异性 SARS-CoV-2 相关公共 TCR 簇之间的 CDR3 序列基序存在不同的模式。我们的结果表明，COVID-19 轻度疾病和肺炎患者的总体 TCR 库谱和 SARS-CoV-2 相关 TCR 簇/克隆型特征存在差异。这些发现为 COVID-19 患者的 TCR 库谱与疾病严重程度之间的相关性提供了重要的见解。
