Biomarkers and Immune Repertoire Metrics Identified by Peripheral Blood Transcriptomic Sequencing Reveal the Pathogenesis of COVID-19.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global crisis; however, our current understanding of the host immune response to SARS-CoV-2 infection remains limited. Herein, we performed RNA sequencing using peripheral blood from acute and convalescent patients and interrogated the dynamic changes of adaptive immune response to SARS-CoV-2 infection over time. Our results revealed numerous alterations in these cohorts in terms of gene expression profiles and the features of immune repertoire. Moreover, a machine learning method was developed and resulted in the identification of five independent biomarkers and a collection of biomarkers that could accurately differentiate and predict the development of COVID-19. Interestingly, the increased expression of one of these biomarkers, UCHL1, a molecule related to nervous system damage, was associated with the clustering of severe symptoms. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T-cell and B-cell responses to SARS-CoV-2 infection, with B-cell response plateaued in the acute phase and declined thereafter, whereas T-cell response can be maintained for up to 6 months post-infection onset and T-cell clonality was positively correlated with the serum level of anti-SARS-CoV-2 IgG. Together, the significantly altered genes or biomarkers, as well as the abnormally high levels of B-cell response in acute infection, may contribute to the pathogenesis of COVID-19 through mediating inflammation and immune responses, whereas prolonged T-cell response in the convalescents might help these patients in preventing reinfection. Thus, our findings could provide insight into the underlying molecular mechanism of host immune response to COVID-19 and facilitate the development of novel therapeutic strategies and effective vaccines.

• Authors: Yang Liu, Yankang Wu, Bing Liu, Youpeng Zhang, Dan San, Yu Chen, Yu Zhou, Long Yu, Haihong Zeng, Yun Zhou, Fuxiang Zhou, Heng Yang, Lei Yin, Yafei Huang
• Journal: Frontiers in immunology (Front Immunol) Vol. 12 Pg. 677025 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 34504487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Liu, Wu, Liu, Zhang, San, Chen, Zhou, Yu, Zeng, Zhou, Zhou, Yang, Yin and Huang.

Chemical References

• Antibodies, Viral
• Biomarkers
• UCHL1 protein, human
• Ubiquitin Thiolesterase

Topics

• Adult
• Aged
• Antibodies, Viral (blood)
• B-Lymphocytes (immunology)
• Biomarkers (blood)
• COVID-19 (blood, genetics, immunology, virology)
• China
• Cohort Studies
• Female
• Humans
• Leukocytes, Mononuclear (chemistry, immunology)
• Machine Learning
• Male
• Middle Aged
• SARS-CoV-2 (physiology)
• Sequence Analysis, RNA
• T-Lymphocytes (immunology)
• Transcriptome
• Ubiquitin Thiolesterase (genetics, immunology)