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J Immunol . Longitudinal Peripheral Blood Transcriptional Analysis Reveals Molecular Signatures of Disease Progression in COVID-19 Patients

tetano

Editor, Senior Moderator
J Immunol


. 2021 Apr 12;ji2001325.
doi: 10.4049/jimmunol.2001325. Online ahead of print.
Longitudinal Peripheral Blood Transcriptional Analysis Reveals Molecular Signatures of Disease Progression in COVID-19 Patients


Qihong Yan[SUP] 1 2 [/SUP], Pingchao Li[SUP] 3 [/SUP], Xianmiao Ye[SUP] 1 [/SUP], Xiaohan Huang[SUP] 1 2 [/SUP], Bo Feng[SUP] 3 [/SUP], Tianxing Ji[SUP] 3 [/SUP], Zhilong Chen[SUP] 4 [/SUP], Feng Li[SUP] 3 [/SUP], Yudi Zhang[SUP] 1 2 [/SUP], Kun Luo[SUP] 1 2 [/SUP], Fengjuan Chen[SUP] 3 [/SUP], Xiaoneng Mo[SUP] 3 [/SUP], Jianhua Wang[SUP] 1 [/SUP], Liqiang Feng[SUP] 1 [/SUP], Fengyu Hu[SUP] 3 [/SUP], Chunliang Lei[SUP] 3 [/SUP], Linbing Qu[SUP] 5 [/SUP], Ling Chen[SUP] 5 3 [/SUP]



Affiliations

Abstract

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients developing severe illness or even death. Disease severity has been associated with increased levels of proinflammatory cytokines and lymphopenia. To elucidate the atlas of peripheral immune response and pathways that might lead to immunopathology during COVID-19 disease course, we performed a peripheral blood RNA sequencing analysis of the same patient's samples collected from symptom onset to full recovery. We found that PBMCs at different disease stages exhibited unique transcriptome characteristics. We observed that SARS-CoV-2 infection caused excessive release of inflammatory cytokines and lipid mediators as well as an aberrant increase of low-density neutrophils. Further analysis revealed an increased expression of RNA sensors and robust IFN-stimulated genes expression but a repressed type I IFN production. SARS-CoV-2 infection activated T and B cell responses during the early onset but resulted in transient adaptive immunosuppression during severe disease state. Activation of apoptotic pathways and functional exhaustion may contribute to the reduction of lymphocytes and dysfunction of adaptive immunity, whereas increase in IL2, IL7, and IL15 may facilitate the recovery of the number and function of lymphocytes. Our study provides comprehensive transcriptional signatures of peripheral blood response in patients with moderate COVID-19.
 
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