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, Nicola K. Wilson, 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, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, 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
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.
Datasets
1. Single-cell multi-omics analysis of the immune response in COVID-19
Metadata
initial_clustering
Resample
Collection_Day
Swab_result
Status
Smoker
Status_on_day_collection
Status_on_day_collection_summary
Days_from_onset
Site
time_after_LPS
Worst_Clinical_Status
Outcome
assay_ontology_term_id
cell_type_ontology_term_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
author_cell_type
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Staff screening26590 cells HsapDv:0000240125732 cells HsapDv:0000239103321 cells HsapDv:000024252699 cells HsapDv:000023852347 cells HsapDv:000024151005 cells HsapDv:000024329673 cells HsapDv:000023727032 cells HsapDv:000016417159 cells HsapDv:000020614086 cells HsapDv:000014611079 cells HsapDv:000016710293 cells HsapDv:000016010187 cells MONDO:0100096527286 cells NCBITaxon:9606647366 cells UBERON:0000178647366 cells CD83_CD14_mono58507 cells B_switched_memory7244 cells Plasma_cell_IgG3527 cells B_non-switched_memory3285 cells Plasma_cell_IgA2699 cells Plasma_cell_IgM1163 cells CD14-positive monocyte120843 cells CD16-positive, CD56-dim natural killer cell, human92848 cells naive thymus-derived CD4-positive, alpha-beta T cell63096 cells effector CD8-positive, alpha-beta T cell53534 cells central memory CD4-positive, alpha-beta T cell49904 cells naive thymus-derived CD8-positive, alpha-beta T cell31175 cells mature NK T cell21673 cells effector memory CD8-positive, alpha-beta T cell18917 cells T-helper 22 cell18379 cells gamma-delta T cell15942 cells T follicular helper cell13608 cells mucosal invariant T cell10992 cells CD16-negative, CD56-bright natural killer cell, human10442 cells class switched memory B cell7244 cells immature B cell5238 cells natural killer cell4963 cells plasmacytoid dendritic cell4612 cells CD14-low, CD16-positive monocyte4140 cells IgG plasma cell3527 cells dendritic cell, human3357 cells unswitched memory B cell3285 cells myeloid dendritic cell3243 cells IgA plasma cell2699 cells effector memory CD4-positive, alpha-beta T cell2634 cells CD34-positive, CD38-negative hematopoietic stem cell2238 cells CD8-positive, alpha-beta T cell1355 cells IgM plasma cell1163 cells erythroid progenitor cell, mammalian773 cells CD4-positive, alpha-beta T cell624 cells regulatory T cell329 cells hematopoietic precursor cell180 cells group 2 innate lymphoid cell, human93 cells myeloid lineage restricted progenitor cell53 cells 10x 3' transcription profiling647366 cells respiratory system disorder15157 cells sixth decade human stage125732 cells fifth decade human stage103321 cells eighth decade human stage52699 cells fourth decade human stage52347 cells seventh decade human stage51005 cells ninth decade human stage29673 cells third decade human stage27032 cells 70-year-old human stage17159 cells 80-year-old human stage14086 cells 52-year-old human stage11079 cells 73-year-old human stage10293 cells 66-year-old human stage10187 cells 38-year-old human stage9429 cells 49-year-old human stage8978 cells 25-year-old human stage7446 cells 56-year-old human stage7221 cells 63-year-old human stage7217 cells 30-year-old human stage6469 cells 76-year-old human stage6163 cells 58-year-old human stage6126 cells 47-year-old human stage5893 cells 59-year-old human stage5731 cells 39-year-old human stage5589 cells 26-year-old human stage4951 cells 44-year-old human stage4752 cells 69-year-old human stage4164 cells 62-year-old human stage4092 cells 65-year-old human stage4019 cells 57-year-old human stage3884 cells 55-year-old human stage3810 cells 21-year-old human stage3408 cells 54-year-old human stage3371 cells 92-year-old human stage3101 cells 64-year-old human stage2897 cells 60-year-old human stage2647 cells 83-year-old human stage2626 cells 31-year-old human stage2614 cells 71-year-old human stage2463 cells 77-year-old human stage2233 cells 87-year-old human stage2040 cells 51-year-old human stage1951 cells 40-year-old human stage1905 cells 68-year-old human stage1661 cells 50-year-old human stage1608 cells 84-year-old human stage1361 cells 46-year-old human stage933 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/ddfad306-714d-4cc0-9985-d9072820c530
Alias names
E-MTAB-10026, EGAS00001005465, PMID33879890, PMC8121667
Cite this study
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. and Kumasaka, N., 2021. Single-cell multi-omics analysis of the immune response in COVID-19. Nature medicine, 27(5), pp.904-916. https://doi.org/10.1038/s41591-021-01329-2
