AUTHOR=Liu Yang , Wu Yankang , Liu Bing , Zhang Youpeng , San Dan , Chen Yu , Zhou Yu , Yu Long , Zeng Haihong , Zhou Yun , Zhou Fuxiang , Yang Heng , Yin Lei , Huang Yafei 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.677025

DOI=10.3389/fimmu.2021.677025

ISSN=1664-3224

ABSTRACT=The COVID-19 pandemic caused by 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 5 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 symptom. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T cell and B cell response 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.