2022, Volume 17, Issue 10
Engineering >> 2022, Volume 17, Issue 10 doi: 10.1016/j.eng.2021.05.009
Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected Patients Through Single-Cell Transcriptome Sequencing
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.
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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 ; Severe infection ; Critically ill ; Monocytes ; Fibrosis
SupplementaryMaterials
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