Single-cell multi-omics analysis of the immune response in COVID-19
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Published:2021-04-20
Issue:5
Volume:27
Page:904-916
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ISSN:1078-8956
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Container-title:Nature Medicine
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language:en
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Short-container-title:Nat Med
Author:
Stephenson Emily, , Reynolds Gary, Botting Rachel A., Calero-Nieto Fernando J.ORCID, Morgan Michael D.ORCID, Tuong Zewen KelvinORCID, Bach Karsten, Sungnak WaradonORCID, Worlock Kaylee B., Yoshida MasahiroORCID, Kumasaka NatsuhikoORCID, Kania Katarzyna, Engelbert Justin, Olabi Bayanne, Spegarova Jarmila StremenovaORCID, Wilson Nicola K.ORCID, Mende NicoleORCID, Jardine Laura, Gardner Louis C. S.ORCID, Goh IssacORCID, Horsfall DaveORCID, McGrath Jim, Webb SimoneORCID, Mather Michael W.ORCID, Lindeboom Rik G. H.ORCID, Dann EmmaORCID, Huang Ni, Polanski KrzysztofORCID, Prigmore Elena, Gothe Florian, Scott Jonathan, Payne Rebecca P.ORCID, Baker Kenneth F.ORCID, Hanrath Aidan T., Schim van der Loeff Ina C. D.ORCID, Barr Andrew S.ORCID, Sanchez-Gonzalez Amada, Bergamaschi Laura, Mescia FedericaORCID, Barnes Josephine L.ORCID, Kilich Eliz, de Wilton Angus, Saigal Anita, Saleh Aarash, Janes Sam M.ORCID, Smith Claire M.ORCID, Gopee Nusayhah, Wilson Caroline, Coupland PaulORCID, Coxhead Jonathan M., Kiselev Vladimir Yu, van Dongen Stijn, Bacardit JaumeORCID, King Hamish W.ORCID, Rostron Anthony J.ORCID, Simpson A. JohnORCID, Hambleton SophieORCID, Laurenti ElisaORCID, Lyons Paul A.ORCID, Meyer Kerstin B.ORCID, Nikolić Marko Z.ORCID, Duncan Christopher J. A., Smith Kenneth G. C.ORCID, Teichmann Sarah A.ORCID, Clatworthy Menna R.ORCID, Marioni John C.ORCID, Göttgens BertholdORCID, Haniffa MuzlifahORCID
Abstract
AbstractAnalysis 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.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
422 articles.
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