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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:27

Enthalten in:

Nature medicine - 27(2021), 5 vom: 15. Mai, Seite 904-916

Sprache:

Englisch

Beteiligte Personen:

Stephenson, Emily [VerfasserIn]
Reynolds, Gary [VerfasserIn]
Botting, Rachel A [VerfasserIn]
Calero-Nieto, Fernando J [VerfasserIn]
Morgan, Michael D [VerfasserIn]
Tuong, Zewen Kelvin [VerfasserIn]
Bach, Karsten [VerfasserIn]
Sungnak, Waradon [VerfasserIn]
Worlock, Kaylee B [VerfasserIn]
Yoshida, Masahiro [VerfasserIn]
Kumasaka, Natsuhiko [VerfasserIn]
Kania, Katarzyna [VerfasserIn]
Engelbert, Justin [VerfasserIn]
Olabi, Bayanne [VerfasserIn]
Spegarova, Jarmila Stremenova [VerfasserIn]
Wilson, Nicola K [VerfasserIn]
Mende, Nicole [VerfasserIn]
Jardine, Laura [VerfasserIn]
Gardner, Louis C S [VerfasserIn]
Goh, Issac [VerfasserIn]
Horsfall, Dave [VerfasserIn]
McGrath, Jim [VerfasserIn]
Webb, Simone [VerfasserIn]
Mather, Michael W [VerfasserIn]
Lindeboom, Rik G H [VerfasserIn]
Dann, Emma [VerfasserIn]
Huang, Ni [VerfasserIn]
Polanski, Krzysztof [VerfasserIn]
Prigmore, Elena [VerfasserIn]
Gothe, Florian [VerfasserIn]
Scott, Jonathan [VerfasserIn]
Payne, Rebecca P [VerfasserIn]
Baker, Kenneth F [VerfasserIn]
Hanrath, Aidan T [VerfasserIn]
Schim van der Loeff, Ina C D [VerfasserIn]
Barr, Andrew S [VerfasserIn]
Sanchez-Gonzalez, Amada [VerfasserIn]
Bergamaschi, Laura [VerfasserIn]
Mescia, Federica [VerfasserIn]
Barnes, Josephine L [VerfasserIn]
Kilich, Eliz [VerfasserIn]
de Wilton, Angus [VerfasserIn]
Saigal, Anita [VerfasserIn]
Saleh, Aarash [VerfasserIn]
Janes, Sam M [VerfasserIn]
Smith, Claire M [VerfasserIn]
Gopee, Nusayhah [VerfasserIn]
Wilson, Caroline [VerfasserIn]
Coupland, Paul [VerfasserIn]
Coxhead, Jonathan M [VerfasserIn]
Kiselev, Vladimir Yu [VerfasserIn]
van Dongen, Stijn [VerfasserIn]
Bacardit, Jaume [VerfasserIn]
King, Hamish W [VerfasserIn]
Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration [VerfasserIn]
Rostron, Anthony J [VerfasserIn]
Simpson, A John [VerfasserIn]
Hambleton, Sophie [VerfasserIn]
Laurenti, Elisa [VerfasserIn]
Lyons, Paul A [VerfasserIn]
Meyer, Kerstin B [VerfasserIn]
Nikolić, Marko Z [VerfasserIn]
Duncan, Christopher J A [VerfasserIn]
Smith, Kenneth G C [VerfasserIn]
Teichmann, Sarah A [VerfasserIn]
Clatworthy, Menna R [VerfasserIn]
Marioni, John C [VerfasserIn]
Göttgens, Berthold [VerfasserIn]
Haniffa, Muzlifah [VerfasserIn]
Baker, Stephen [Sonstige Person]
Bradley, John R [Sonstige Person]
Dougan, Gordon [Sonstige Person]
Goodfellow, Ian G [Sonstige Person]
Gupta, Ravindra K [Sonstige Person]
Hess, Christoph [Sonstige Person]
Kingston, Nathalie [Sonstige Person]
Lehner, Paul J [Sonstige Person]
Matheson, Nicholas J [Sonstige Person]
Owehand, Willem H [Sonstige Person]
Saunders, Caroline [Sonstige Person]
Smith, Kenneth G C [Sonstige Person]
Summers, Charlotte [Sonstige Person]
Thaventhiran, James E D [Sonstige Person]
Toshner, Mark [Sonstige Person]
Weekes, Michael P [Sonstige Person]
Bucke, Ashlea [Sonstige Person]
Calder, Jo [Sonstige Person]
Canna, Laura [Sonstige Person]
Domingo, Jason [Sonstige Person]
Elmer, Anne [Sonstige Person]
Fuller, Stewart [Sonstige Person]
Harris, Julie [Sonstige Person]
Hewitt, Sarah [Sonstige Person]
Kennet, Jane [Sonstige Person]
Jose, Sherly [Sonstige Person]
Kourampa, Jenny [Sonstige Person]
Meadows, Anne [Sonstige Person]
O'Brien, Criona [Sonstige Person]
Price, Jane [Sonstige Person]
Publico, Cherry [Sonstige Person]
Rastall, Rebecca [Sonstige Person]
Ribeiro, Carla [Sonstige Person]
Rowlands, Jane [Sonstige Person]
Ruffolo, Valentina [Sonstige Person]
Tordesillas, Hugo [Sonstige Person]
Bullman, Ben [Sonstige Person]
Dunmore, Benjamin J [Sonstige Person]
Fawke, Stuart [Sonstige Person]
Gräf, Stefan [Sonstige Person]
Hodgson, Josh [Sonstige Person]
Huang, Christopher [Sonstige Person]
Hunter, Kelvin [Sonstige Person]
Jones, Emma [Sonstige Person]
Legchenko, Ekaterina [Sonstige Person]
Matara, Cecilia [Sonstige Person]
Martin, Jennifer [Sonstige Person]
O'Donnell, Ciara [Sonstige Person]
Pointon, Linda [Sonstige Person]
Pond, Nicole [Sonstige Person]
Shih, Joy [Sonstige Person]
Sutcliffe, Rachel [Sonstige Person]
Tilly, Tobias [Sonstige Person]
Treacy, Carmen [Sonstige Person]
Tong, Zhen [Sonstige Person]
Wood, Jennifer [Sonstige Person]
Wylot, Marta [Sonstige Person]
Betancourt, Ariana [Sonstige Person]
Bower, Georgie [Sonstige Person]
De Sa, Aloka [Sonstige Person]
Epping, Madeline [Sonstige Person]
Huhn, Oisin [Sonstige Person]
Jackson, Sarah [Sonstige Person]
Jarvis, Isobel [Sonstige Person]
Marsden, Jimmy [Sonstige Person]
Nice, Francesca [Sonstige Person]
Okecha, Georgina [Sonstige Person]
Omarjee, Ommar [Sonstige Person]
Perera, Marianne [Sonstige Person]
Richoz, Nathan [Sonstige Person]
Sharma, Rahul [Sonstige Person]
Turner, Lori [Sonstige Person]
De Bie, Eckart M D D [Sonstige Person]
Bunclark, Katherine [Sonstige Person]
Josipovic, Masa [Sonstige Person]
Mackay, Michael [Sonstige Person]
Michael, Alice [Sonstige Person]
Rossi, Sabrina [Sonstige Person]
Selvan, Mayurun [Sonstige Person]
Spencer, Sarah [Sonstige Person]
Yong, Cissy [Sonstige Person]
Ansaripour, Ali [Sonstige Person]
Mwaura, Lucy [Sonstige Person]
Patterson, Caroline [Sonstige Person]
Polwarth, Gary [Sonstige Person]
Polgarova, Petra [Sonstige Person]
Stefano, Giovanni di [Sonstige Person]
Allison, John [Sonstige Person]
Butcher, Helen [Sonstige Person]
Caputo, Daniela [Sonstige Person]
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Dewhurst, Eleanor [Sonstige Person]
Furlong, Anita [Sonstige Person]
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Ivers, Tasmin [Sonstige Person]
Kasanicki, Mary [Sonstige Person]
Gresley, Emma Le [Sonstige Person]
Linger, Rachel [Sonstige Person]
Meloy, Sarah [Sonstige Person]

Links:

Volltext

Themen:

Journal Article
Proteome
Receptors, Antigen, B-Cell
Receptors, Antigen, T-Cell
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 24.05.2021

Date Revised 27.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1038/s41591-021-01329-2

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM324342802