摘要
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-19samples 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 severedisease-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.
基金
supported by the National Science and Technology Major Project(2017ZX10204401001002)
the National Key Research and Development Project of China(2017ZX10204401001002008)
the Key Research and Development Project of Zhejiang Province(2020C03123)
Zhejiang Provincial Nature Science Foundation of China(LED20H19001)。
