Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.


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Stephenson, E., Reynolds, G., Botting, R., Calero-Nieto, F., Morgan, M., Tuong, Z., Bach, K., Sungnak, W., Worlock, K., Yoshida, M., Kumasaka, N., Kania, K., Engelbert, J., Olabi, B., Spegarova, J., Mende, N., Jardine, L., Gardner, L., Goh, I., Horsfall, D., McGrath, J., Webb, S., Mather, M., Lindeboom, R., Dann, E., Huang, N., Polanski, K., Prigmore, E., Gothe, F., Scott, J., Payne, R., Baker, K., Hanrath, A., Loeff, I., Barr, A., Sanchez-Gonzalez, A., Bergamaschi, L., Mescia, F., Barnes, J., Kilich, E., Wilton, A., Saigal, A., Saleh, A., Janes, S., Smith, C., Gopee, N., Wilson, C., Coupland, P., Coxhead, J., Kiselev, V., Dongen, S., Bacardit, J., King, H., Rostron, A., Simpson, A., Hambleton, S., Laurenti, E., Lyons, P., Meyer, K., Nikolić, M., Duncan, C., Smith, K., Teichmann, S., Clatworthy, M., Marioni, J., Göttgens, B. & Haniffa, M. 2021, 'Single-cell multi-omics analysis of the immune response in COVID-19', Nature Medicine, 27, pp. 904-916. https://doi.org/10.1038/s41591-021-01329-2

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Last updated: 29 June 2023
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