T cell receptor repertoires as potential diagnostic markers for patients with COVID-19

Hou, Xianliang; Fan, Wentao; Wang, Guangyu; Chen, Xiaoyan; Mo, Chune; Wang, Yongsi; Gong, Weiwei; Wen, Xuyan; Chen, Hui; He, Dan; Mo, Lijun; Jiang, Shaofeng; Ou, Minglin; Guo, Haonan; Liu, Hongbo

Objective Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. T cell receptor (TCR) are crucial mediators of antiviral adaptive immunity. Here, we sought to comprehensively characterize the TCR repertoire changes in patients with COVID-19. Design We implemented a large sample size multi-center randomized controlled trial to study the TCR repertoire features, and identify COVID-19 disease-related TCR sequences. Results We found that some TCRβ features of COVID-19 patients were remarkably different from that of healthy control, including decreased repertoire diversity, longer CDR3 length, skewed utilization of the TRBV/J, and a high degree of TCRβ sharing. Moreover, this analysis showed TCR repertoire diversity declines with aging, which may be a cause of higher infection and mortality in elderly patients. Importantly we identified a set of TCRβ clones, which can distinguish COVID-19 patients from healthy controls with high accuracy. Notably, this diagnostic model demonstrates 100% specificity and 82.68% sensitivity at 0-3 days post diagnosis. Conclusions This study lay the foundation for immunodiagnosis and the development of medicines and vaccines for COVID-19 patients.