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

• Published in: International journal of infectious diseases Vol. 113; pp. 308 - 317
• Main Authors: Hou, Xianliang, Wang, Guangyu, Fan, Wentao, Chen, Xiaoyan, Mo, Chune, Wang, Yongsi, Gong, Weiwei, Wen, Xuyan, Chen, Hui, He, Dan, Mo, Lijun, Jiang, Shaofeng, Ou, Minglin, Guo, Haonan, Liu, Hongbo
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01-12-2021; The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases; Elsevier
• Subjects: Adaptive immunity; Aging; Case-Control Studies; Coronavirus disease 2019; COVID-19 - diagnosis; COVID-19 - immunology; Humans; Receptors, Antigen, T-Cell, alpha-beta - genetics; SARS-CoV-2; T-cell receptor; TRBJ; BWNW; TCR; Coronavirus disease 2019; HUniv12Oct; TCRβ; Adaptive immunity; DLS; T-cell receptor; COVID-19; SARS-CoV-2; TRBV; HC; CDR3
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2021.10.033

•Decreased TCR repertoire diversity and longer CDR3 length were found in COVID-19 patients.•TRBV/J gene usage and overlap indices are abnormal in COVID-19 patients.•CDR3 length and recombination events are abnormal in COVID-19 patients.•Disease-associated TCRβ clones are useful in the diagnosis of COVID-19.
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.