Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients
Ren, X.; Wen, W.; Fan, X.; Hou, W.; Su, B.; Cai, P.; Li, J.; Liu, Y.; Tang, F.; Zhang, F.; Yang, Y.; He, J.; Ma, W.; He, J.; Wang, P.; Cao, Q.; Chen, F.; Chen, Y.; Cheng, X.; Deng, G.; Deng, X.; Ding, W.; Feng, Y.; Gan, R.; Guo, C.; Guo, W.; He, S.; Jiang, C.; Liang, J.; Li, Y.-M.; Lin, J.; Ling, Y.; Liu, H.; Liu, J.; Liu, N.; Liu, Y.; Luo, M.; Ma, Q.; Song, Q.; Sun, W.; Wang, G.; Wang, F.; Wang, Y.; Wen, X.; Wu, Q.; Xu, G.; Xie, X.; Xiong, X.; Xing, X.; Xu, H.; Yin, C.; Yu, D.; Yu, K.; Yuan, J.; Zhang, B.; Zhang, T.; Zhao, J.; Zhao, P.; Zhou, J.; Zhou, W.; Zhong, S.; Zhong, X.; Zhang, S.; Zhu
Show abstract
Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI
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