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.; 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.; 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

doi:10.1101/2020.10.29.360479

bioRxiv · 10.1101/2020.10.29.360479

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.·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.·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

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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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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., 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., 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. 2020-10-29. Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients. https://doi.org/10.1101/2020.10.29.360479

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