Journal Article

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

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

2021

Overview

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. Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/514/1949 / 631/250/232 / 631/250/254 / 631/326/596/4130 / 692/699/255/2514 / Alveoli / Antigens / Biomedical and Life Sciences / Biomedicine / Blood / Cancer Research / CD16 antigen / CD34 antigen / CD8 antigen / Cell activation / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - immunology / Cross-Sectional Studies / Effector cells / Gene expression / Hematopoietic stem cells / Humans / Immune response / Immune system / Immunological memory / Infectious Diseases / Leukocytes (mononuclear) / Lymphocytes / Lymphocytes B / Lymphocytes T / Macrophages / Memory cells / Metabolic Diseases / Molecular Medicine / Monocytes / Monocytes - immunology / Neurosciences / Pathogenesis / Peripheral blood mononuclear cells / Plasma cells / Platelets / Progenitor cells / Proteome / Proteomes / Proteomics / Receptors, Antigen, B-Cell - immunology / Receptors, Antigen, T-Cell - immunology / Respiratory diseases / SARS-CoV-2 - immunology / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Single-Cell Analysis - methods / T-Lymphocytes - immunology / Transcriptome / Transcriptomes / Viral diseases