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

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

doi:10.1038/s41591-021-01329-2

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

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

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Abstract

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.

Original language	English
Pages (from-to)	904-916
Number of pages	13
Journal	Nature Medicine
Volume	27
DOIs	https://doi.org/10.1038/s41591-021-01329-2
Publication status	Published - 20 Apr 2021

Data Availability Statement

The dataset from our study can be explored interactively through the web portal https://covid19cellatlas.org/. The data object, as a h5ad file, can also be downloaded from https://covid19cellatlas.org/. The processed data are available to download from Array Express under accession number E-MTAB-10026. Source data are provided with this paper.

All data analysis scripts are available on https://github.com/scCOVID-19/COVIDPBMC/.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Stephenson, E., Reynolds, G., Botting, R. A., Calero-Nieto, F. J., Morgan, M. D., Tuong, Z. K., Bach, K., Sungnak, W., Worlock, K. B., Yoshida, M., Kumasaka, N., Kania, K., Engelbert, J., Olabi, B., Spegarova, J. S., Mende, N., Jardine, L., Gardner, L. C. S., Goh, I., ... Haniffa, M. (2021). Single-cell multi-omics analysis of the immune response in COVID-19. Nature Medicine, 27, 904-916. https://doi.org/10.1038/s41591-021-01329-2

Stephenson, E, Reynolds, G, Botting, RA, Calero-Nieto, FJ, Morgan, MD, Tuong, ZK, Bach, K, Sungnak, W, Worlock, KB, Yoshida, M, Kumasaka, N, Kania, K, Engelbert, J, Olabi, B, Spegarova, JS, Mende, N, Jardine, L, Gardner, LCS, Goh, I, Horsfall, D, McGrath, J, Webb, S, Mather, MW, Lindeboom, RGH, Dann, E, Huang, N, Polanski, K, Prigmore, E, Gothe, F, Scott, J, Payne, RP, Baker, KF, Hanrath, AT, Loeff, ICDSVD, Barr, AS, Sanchez-Gonzalez, A, Bergamaschi, L, Mescia, F, Barnes, JL, Kilich, E, Wilton, AD, Saigal, A, Saleh, A, Janes, SM, Smith, CM, Gopee, N, Wilson, C, Coupland, P, Coxhead, JM, Kiselev, VY, Dongen, SV, Bacardit, J, King, HW, Rostron, AJ, Simpson, AJ, Hambleton, S, Laurenti, E, Lyons, PA, Meyer, KB, Nikolić, MZ, Duncan, CJA, Smith, KGC, Teichmann, SA, Clatworthy, MR, Marioni, JC, Göttgens, B & Haniffa, M 2021, 'Single-cell multi-omics analysis of the immune response in COVID-19', Nature Medicine, vol. 27, pp. 904-916. https://doi.org/10.1038/s41591-021-01329-2

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abstract = "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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AU - Botting, Rachel A.

AU - Calero-Nieto, Fernando J.

AU - Morgan, Michael D.

AU - Tuong, Zewen Kelvin

AU - Bach, Karsten

AU - Sungnak, Waradon

AU - Worlock, Kaylee B.

AU - Yoshida, Masahiro

AU - Kumasaka, Natsuhiko

AU - Kania, Katarzyna

AU - Engelbert, Justin

AU - Olabi, Bayanne

AU - Spegarova, Jarmila Stremenova

AU - Mende, Nicole

AU - Jardine, Laura

AU - Gardner, Louis C. S.

AU - Goh, Issac

AU - Horsfall, Dave

AU - McGrath, Jim

AU - Webb, Simone

AU - Mather, Michael W.

AU - Lindeboom, Rik G. H.

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AU - Barr, Andrew S.

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AU - Barnes, Josephine L.

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AU - Saleh, Aarash

AU - Janes, Sam M.

AU - Smith, Claire M.

AU - Gopee, Nusayhah

AU - Wilson, Caroline

AU - Coupland, Paul

AU - Coxhead, Jonathan M.

AU - Kiselev, Vladimir Yu

AU - Dongen, Stijn van

AU - Bacardit, Jaume

AU - King, Hamish W.

AU - Rostron, Anthony J.

AU - Simpson, A. John

AU - Hambleton, Sophie

AU - Laurenti, Elisa

AU - Lyons, Paul A.

AU - Meyer, Kerstin B.

AU - Nikolić, Marko Z.

AU - Duncan, Christopher J. A.

AU - Smith, Kenneth G. C.

AU - Teichmann, Sarah A.

AU - Clatworthy, Menna R.

AU - Marioni, John C.

AU - Göttgens, Berthold

AU - Haniffa, Muzlifah

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JO - Nature Medicine

JF - Nature Medicine

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

Abstract

Data Availability Statement

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