Longitudinal Analysis of T and B Cell Receptor Repertoire Transcripts Reveal Dynamic Immune Response in COVID-19 Patients

• Published in: Frontiers in immunology Vol. 11; p. 582010
• Main Authors: Niu, Xuefeng, Li, Song, Li, Pingchao, Pan, Wenjing, Wang, Qian, Feng, Ying, Mo, Xiaoneng, Yan, Qihong, Ye, Xianmiao, Luo, Jia, Qu, Linbing, Weber, Daniel, Byrne-Steele, Miranda L., Wang, Zhe, Yu, Fengjia, Li, Fang, Myers, Richard M., Lotze, Michael T., Zhong, Nanshan, Han, Jian, Chen, Ling
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 30.09.2020
• Subjects: Adult; Aged; Aged, 80 and over; B cell receptor; B-Lymphocytes - immunology; Betacoronavirus - immunology; biomarker; CD4 Lymphocyte Count; Coronavirus Infections - immunology; Coronavirus Infections - pathology; COVID-19; Female; High-Throughput Nucleotide Sequencing; Humans; immune repertoire; Immunology; Lymphopenia - pathology; Male; Middle Aged; Pandemics; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, T-Cell - genetics; SARS-CoV-2; T cell receptor; T-Lymphocytes - immunology; COVID-19; SARS-CoV-2; immune repertoire; T cell receptor; B cell receptor; biomarker
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.582010

Severe COVID-19 is associated with profound lymphopenia and an elevated neutrophil to lymphocyte ratio. We applied a novel dimer avoidance multiplexed polymerase chain reaction next-generation sequencing assay to analyze T (TCR) and B cell receptor (BCR) repertoires. Surprisingly, TCR repertoires were markedly diminished during the early onset of severe disease but recovered during the convalescent stage. Monitoring TCR repertoires could serve as an indicative biomarker to predict disease progression and recovery. Panoramic concurrent assessment of BCR repertoires demonstrated isotype switching and a transient but dramatic early IgA expansion. Dominant B cell clonal expansion with decreased diversity occurred following recovery from infection. Profound changes in T cell homeostasis raise critical questions about the early events in COVID-19 infection and demonstrate that immune repertoire analysis is a promising method for evaluating emergent host immunity to SARS-CoV-2 viral infection, with great implications for assessing vaccination and other immunological therapies.