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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
Yan Zhang, Shuting Wang, He Xia, Jing Guo, Kangxin He, Chenjie Huang, Rui Luo, Yanfei Chen, Kaijin Xu, Hainv Gao, Jifang Sheng, Lanjuan Li
工程（英文） ›› 2022, Vol. 17 ›› Issue (10) : 161-169.
PDF(2905 KB)
PDF(2905 KB)
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
Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected Patients Through Single-Cell Transcriptome Sequencing
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。
Understanding the immunological characteristics of monocytes—including the characteristics associated with fibrosis—in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.
COVID-19 / 重症感染 / 危重症 / 单核细胞 / 纤维化
COVID-19 / Severe infection / Critically ill / Monocytes / Fibrosis
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