Single-cell multi-omics analysis of the immune response in COVID-19

Stephenson, Emily; Reynolds, Gary; Botting, Rachel A.; Calero-Nieto, Fernando J.; Morgan, Michael D.; Tuong, Zewen Kelvin; Bach, Karsten; Sungnak, Waradon; Worlock, Kaylee B.; Yoshida, Masahiro; Kumasaka, Natsuhiko; Kania, Katarzyna; Engelbert, Justin; Olabi, Bayanne; Spegarova, Jarmila Stremenova; Wilson, Nicola K.; Mende, Nicole; Jardine, Laura; Gardner, Louis C. S.; Goh, Issac; Horsfall, Dave; McGrath, Jim; Webb, Simone; Mather, Michael W.; Lindeboom, Rik G. H.; Dann, Emma; Huang, Ni; Polanski, Krzysztof; Prigmore, Elena; Gothe, Florian; Scott, Jonathan; Payne, Rebecca P.; Baker, Kenneth F.; Hanrath, Aidan T.; Schim van der Loeff, Ina C. D.; Barr, Andrew S.; Sanchez-Gonzalez, Amada; Bergamaschi, Laura; Mescia, Federica; Barnes, Josephine L.; Kilich, Eliz; de Wilton, Angus; Saigal, Anita; Saleh, Aarash; Janes, Sam M.; Smith, Claire M.; Gopee, Nusayhah; Wilson, Caroline; Coupland, Paul; Coxhead, Jonathan M.; Kiselev, Vladimir Yu; van Dongen, Stijn; Bacardit, Jaume; King, Hamish W.; Rostron, Anthony J.; Simpson, A. John; Hambleton, Sophie; Laurenti, Elisa; Lyons, Paul A.; Meyer, Kerstin B.; Nikolić, Marko Z.; Duncan, Christopher J. A.; Smith, Kenneth G. C.; Teichmann, Sarah A.; Clatworthy, Menna R.; Marioni, John C.; Göttgens, Berthold; Haniffa, Muzlifah

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.