Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, the Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China.
College of Laboratory Medicine, Guilin Medical University, Guilin, 541199, China.
Int J Infect Dis. 2021 Dec;113:308-317. doi: 10.1016/j.ijid.2021.10.033. Epub 2021 Oct 22.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health emergency. T-cell receptors (TCRs) are crucial mediators of antiviral adaptive immunity. This study sought to comprehensively characterize the TCR repertoire changes in patients with COVID-19.
A large sample size multi-center randomized controlled trial was implemented to study the features of the TCR repertoire and identify COVID-19 disease-related TCR sequences.
It was found that some T-cell receptor beta chain (TCRβ) features differed markedly between COVID-19 patients and healthy controls, including decreased repertoire diversity, longer complementarity-determining region 3 (CDR3) length, skewed utilization of the TCRβ variable gene/joining gene (TRBV/J), and a high degree of TCRβ sharing in COVID-19 patients. Moreover, this analysis showed that TCR repertoire diversity declines with aging, which may be a cause of the higher infection and mortality rates in elderly patients. Importantly, a set of TCRβ clones that can distinguish COVID-19 patients from healthy controls with high accuracy was identified. Notably, this diagnostic model demonstrates 100% specificity and 82.68% sensitivity at 0-3 days post diagnosis.
This study lays the foundation for immunodiagnosis and the development of medicines and vaccines for COVID-19 patients.
由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）是一场持续的全球卫生紧急事件。T 细胞受体（TCRs）是抗病毒适应性免疫的关键介质。本研究旨在全面描述 COVID-19 患者的 TCR 库变化。
实施了一项大型样本量多中心随机对照试验，以研究 TCR 库的特征，并确定与 COVID-19 疾病相关的 TCR 序列。
研究发现 COVID-19 患者与健康对照之间存在一些 T 细胞受体β链（TCRβ）特征明显不同，包括 repertoire 多样性降低、互补决定区 3（CDR3）长度变长、TCRβ可变基因/连接基因（TRBV/J）的利用偏斜以及 COVID-19 患者中 TCRβ 的高度共享。此外，该分析表明 TCR 库多样性随年龄增长而下降，这可能是老年患者感染率和死亡率较高的原因。重要的是，确定了一组 TCRβ 克隆，可准确地区分 COVID-19 患者与健康对照。值得注意的是，该诊断模型在诊断后 0-3 天内具有 100%的特异性和 82.68%的敏感性。
本研究为 COVID-19 患者的免疫诊断以及药物和疫苗的开发奠定了基础。
