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Isolating Human Peripheral Blood Mononuclear Cells and CD4+ T cells from Sézary Syndrome Patients for Transcriptomic Profiling
Published on: October 14, 2021
Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected Patients Through
Yan Zhang1, Shuting Wang1, He Xia1
1State 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.
Insights
Researchers identified two new monocyte subsets, Mono 0 and Mono 5, in severe COVID-19 patients. These cells show pro-fibrotic and pro-inflammatory traits, offering potential targets for treating severe coronavirus disease 2019.
Area of Science:
- Immunology
- Genomics
- Pathology
Background:
- Severe coronavirus disease 2019 (COVID-19) pathogenesis involves complex immunological responses.
- Understanding monocyte behavior, particularly pro-fibrotic characteristics, is key to managing disease severity.
Purpose of the Study:
- To investigate the immunological characteristics of monocytes in severe COVID-19.
- To identify novel monocyte subsets associated with severe disease and fibrosis.
Main Methods:
- Single-cell transcriptomic sequencing of peripheral blood from healthy controls and COVID-19 patients (severe, moderate, convalescent).
- Analysis of monocyte populations, gene expression (AREG, EREG, IL-18), and signaling pathways (ErbB, HIF-1).
Main Results:
- Severe COVID-19 patients exhibited remodeled monocytes with increased proportion and reduced diversity.
- Two novel severe-disease-specific monocyte subsets (Mono 0 and Mono 5) were identified, expressing AREG, EREG, and IL-18.
- These subsets showed enriched ErbB signaling, pro-fibrogenic/pro-inflammatory characteristics, and altered metabolism (glycolysis, HIF-1 pathway).
Conclusions:
- Discovery of two novel monocyte subsets (Mono 0, Mono 5) as potential predictors and therapeutic targets for severe COVID-19.
- Identification of specific gene expression and metabolic pathways linked to severe COVID-19 monocyte dysfunction.
- Provides a resource for further research into COVID-19 pathogenesis and treatment strategies.
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.
