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

Autor: 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., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, Haniffa, Muzlifah, Baker, Stephen, Bradley, John R., Dougan, Gordon, Goodfellow, Ian G., Gupta, Ravindra K., Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Smith, Kenneth G. C., Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, De Sa, Aloka, Epping, Madeline, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Marsden, Jimmy, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Sharma, Rahul, Turner, Lori, De Bie, Eckart M. D. D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Stefano, Giovanni Di, Allison, John, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Gresley, Emma Le, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer
Přispěvatelé: Calero-Nieto, Fernando J. [0000-0003-3358-8253], Morgan, Michael D. [0000-0003-0757-0711], Tuong, Zewen Kelvin [0000-0002-6735-6808], Sungnak, Waradon [0000-0002-0136-4960], Yoshida, Masahiro [0000-0002-3521-5322], Kumasaka, Natsuhiko [0000-0002-3557-0375], Spegarova, Jarmila Stremenova [0000-0002-0710-9266], Wilson, Nicola K. [0000-0003-0865-7333], Mende, Nicole [0000-0002-5078-2333], Gardner, Louis C. S. [0000-0002-7200-978X], Goh, Issac [0000-0002-6397-3518], Horsfall, Dave [0000-0002-8086-812X], Webb, Simone [0000-0003-3058-8952], Mather, Michael W. [0000-0001-7972-7111], Lindeboom, Rik G. H. [0000-0002-3660-504X], Dann, Emma [0000-0002-7400-7438], Polanski, Krzysztof [0000-0002-2586-9576], Payne, Rebecca P. [0000-0002-9037-7367], Baker, Kenneth F. [0000-0002-6735-2911], Schim van der Loeff, Ina C. D. [0000-0003-1196-6196], Barr, Andrew S. [0000-0002-8084-7644], Mescia, Federica [0000-0002-2759-4027], Barnes, Josephine L. [0000-0001-9938-3176], Janes, Sam M. [0000-0002-6634-5939], Smith, Claire M. [0000-0002-8913-0009], Coupland, Paul [0000-0002-2871-3374], Bacardit, Jaume [0000-0002-2692-7205], King, Hamish W. [0000-0001-5972-8926], Rostron, Anthony J. [0000-0002-9336-1723], Simpson, A. John [0000-0003-4731-7294], Hambleton, Sophie [0000-0001-7954-3267], Laurenti, Elisa [0000-0002-9917-9092], Lyons, Paul A. [0000-0001-7035-8997], Meyer, Kerstin B. [0000-0001-5906-1498], Nikolić, Marko Z. [0000-0001-6304-6848], Smith, Kenneth G. C. [0000-0003-3829-4326], Teichmann, Sarah A. [0000-0002-6294-6366], Clatworthy, Menna R. [0000-0002-3340-9828], Marioni, John C. [0000-0001-9092-0852], Göttgens, Berthold [0000-0001-6302-5705], Haniffa, Muzlifah [0000-0002-3927-2084], Apollo - University of Cambridge Repository
Rok vydání: 2021
Předmět:
DOI: 10.17863/cam.70127
Popis: Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255
Funder: University College London, Birkbeck MRC Doctoral Training Programme
Funder: The Jikei University School of Medicine
Funder: Action Medical Research (GN2779)
Funder: NIHR Clinical Lectureship (CL-2017-01-004)
Funder: NIHR (ACF-2018-01-004) and the BMA Foundation
Funder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)
Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)
Funder: Barbour Foundation
Funder: ERC Consolidator and EU MRG-Grammar awards
Funder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)
Funder: European Molecular Biology Laboratory (EMBL)
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.
Databáze: OpenAIRE
Externí odkaz: