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.