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《工程(英文)》 >> 2022年 第17卷 第10期 doi: 10.1016/j.eng.2021.05.009

单细胞转录组测序鉴定COVID-19外周血重症疾病特异性单核细胞

a State Key Laboratory for Diagnosis and Treatment of Infectious Disease, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
b Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310022, China

# These authors contributed equally to this work.

收稿日期: 2021-01-22 修回日期: 2021-05-07 录用日期: 2021-05-17 发布日期: 2021-06-12

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摘要

了解重症新型冠状病毒肺炎(COVID-19)患者单核细胞的免疫学特征(包括与纤维化相关的特征)对了解疾病的重症化机制和阻止疾病恶化至关重要。本研究共纳入7名COVID-19患者(包括3名重症/危重症患者和4名普通型患者)和6名健康对照者。采集7名COVID-19患者不同疾病时期外周血样本,包括重症/危重症时期血样3例,轻症时期血样4例,康复期血样7例。将以上血样和6例健康对照者血样进行单细胞转录组测序分析。本研究发现在COVID-19重症/危重症时期,单核细胞发生显著变化。单核细胞在外周血单个核细胞中占比增加,多样性却显著降低。同时本研究发现两个新的COVID-19重症疾病特异性单核细胞亚群:Mono 0和Mono 5。这两个亚群表达amphiregulin(AREG)、epiregulin(EREG)和细胞因子基因IL-18,KEGG分析显示富集的ErbB信号通路,这两个亚群可能具有促纤维化和促炎的特征。进一步分析发现Mono 0和Mono 5发生代谢改变,包括糖酵解/糖异生的增加和HIF-1信号通路的增加。本研究同时发现一个疾病重症前期取得的样本显示出与重症/危重症时期样本相似的单核细胞UMAP图谱。本研究发现了两种新的COVID-19重症疾病特异性单核细胞亚群,可作为重症COVID-19的潜在预测因子和治疗靶点。

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