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Engineering (Beijing) . Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected patients Through Single-Cell T

tetano

Editor, Senior Moderator
Engineering (Beijing)


. 2021 Jun 12.
doi: 10.1016/j.eng.2021.05.009. Online ahead of print.
Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected patients Through Single-Cell Transcriptome Sequencing


Yan Zhang[SUP] 1 [/SUP], Shuting Wang[SUP] 1 [/SUP], He Xia[SUP] 1 [/SUP], Jing Guo[SUP] 1 [/SUP], Kangxin He[SUP] 1 [/SUP], Chenjie Huang[SUP] 1 [/SUP], Rui Luo[SUP] 1 [/SUP], Yanfei Chen[SUP] 1 [/SUP], Kaijin Xu[SUP] 1 [/SUP], Hainv Gao[SUP] 2 [/SUP], Jifang Sheng[SUP] 1 [/SUP], Lanjuan Li[SUP] 1 [/SUP]



Affiliations

Abstract

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.

Keywords: COVID-19; Critically ill; Fibrosis; Monocytes; Severe infection.
 
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