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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.
Highlights
The outbreak of coronavirus disease 2019 (COVID-19), first reported in the city of Wuhan, China, in December 2019, has posed formidable threat to global public health [1,2,3]
A total of 62 COVID-19 convalescents, acute patients, and healthy donors were involved in this study
We found that ubiquitin C-terminal hydrolase L1 (UCHL1) expression used as a biomarker in the peripheral blood can predict the disease development of COVID-19, the potential mechanism by which this molecule participates in the pathogenesis of COVID-19 requires further investigations
Summary
The outbreak of coronavirus disease 2019 (COVID-19), first reported in the city of Wuhan, China, in December 2019, has posed formidable threat to global public health [1,2,3]. The clinical manifestations after SARSCoV-2 infection are heterogeneous between individuals, ranging from asymptomatic, development of multiple symptoms such as coughing and fever, to failure of the respiratory system, and even death [13,14,15]. This infection results in mild illness in most of the cases; approximately 15% of the patients need hospitalization, while nearly 5% of the patients develop acute respiratory syndrome and have high mortality, especially in the elderly and patients with underlying diseases [16]. There is an urgent need to develop novel therapeutic agents and effective vaccines for controlling the current pandemic, which requires the elucidation of the pathogenesis of COVID-19
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