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

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 we...

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Published inFrontiers 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.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.
Author Wang, Zhe
Li, Song
Qu, Linbing
Niu, Xuefeng
Li, Fang
Lotze, Michael T.
Li, Pingchao
Zhong, Nanshan
Feng, Ying
Ye, Xianmiao
Han, Jian
Luo, Jia
Mo, Xiaoneng
Byrne-Steele, Miranda L.
Weber, Daniel
Wang, Qian
Yan, Qihong
Pan, Wenjing
Yu, Fengjia
Chen, Ling
Myers, Richard M.
AuthorAffiliation 5 HudsonAlpha Institute for Biotechnology , Huntsville, AL , United States
6 Guangzhou Eighth People’s Hospital, Guangzhou Medical University , Guangzhou , China
3 iRepertoire Inc. , Huntsville, AL , United States
7 Department of Surgery, University of Pittsburgh Medical Center , Pittsburgh, PA , United States
2 Jiangsu Industrial Technology Research Institute (JITRI), Applied Adaptome Immunology Institute , Nanjing , China
1 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University , Guangzhou , China
4 Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL), Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou , China
AuthorAffiliation_xml – name: 4 Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL), Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou , China
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– name: 7 Department of Surgery, University of Pittsburgh Medical Center , Pittsburgh, PA , United States
– name: 1 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University , Guangzhou , China
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Copyright Copyright © 2020 Niu, Li, Li, Pan, Wang, Feng, Mo, Yan, Ye, Luo, Qu, Weber, Byrne-Steele, Wang, Yu, Li, Myers, Lotze, Zhong, Han and Chen.
Copyright © 2020 Niu, Li, Li, Pan, Wang, Feng, Mo, Yan, Ye, Luo, Qu, Weber, Byrne-Steele, Wang, Yu, Li, Myers, Lotze, Zhong, Han and Chen 2020 Niu, Li, Li, Pan, Wang, Feng, Mo, Yan, Ye, Luo, Qu, Weber, Byrne-Steele, Wang, Yu, Li, Myers, Lotze, Zhong, Han and Chen
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Keywords COVID-19
SARS-CoV-2
immune repertoire
T cell receptor
B cell receptor
biomarker
Language English
License Copyright © 2020 Niu, Li, Li, Pan, Wang, Feng, Mo, Yan, Ye, Luo, Qu, Weber, Byrne-Steele, Wang, Yu, Li, Myers, Lotze, Zhong, Han and Chen.
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Reviewed by: Yu Nee Lee, Sheba Medical Center, Israel; James M. Heather, Massachusetts General Hospital and Harvard Medical School, United States
These authors have contributed equally to this work
Edited by: Lucia Lopalco, San Raffaele Hospital (IRCCS), Italy
This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology
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Snippet Severe COVID-19 is associated with profound lymphopenia and an elevated neutrophil to lymphocyte ratio. We applied a novel dimer avoidance multiplexed...
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SubjectTerms 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
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Title Longitudinal Analysis of T and B Cell Receptor Repertoire Transcripts Reveal Dynamic Immune Response in COVID-19 Patients
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