King's College London

Research portal

A dynamic COVID-19 immune signature includes associations with poor prognosis

Research output: Contribution to journalArticlepeer-review

Adam G. Laing, Anna Lorenc, Irene del Molino del Barrio, Abhishek Das, Matthew Fish, Leticia Monin, Miguel Muñoz-Ruiz, Duncan R. McKenzie, Thomas S. Hayday, Isaac Francos-Quijorna, Shraddha Kamdar, Magdalene Joseph, Daniel Davies, Richard Davis, Aislinn Jennings, Iva Zlatareva, Pierre Vantourout, Yin Wu, Vasiliki Sofra, Florencia Cano & 30 more Maria Greco, Efstathios Theodoridis, Joshua Freedman, Sarah Gee, Julie Nuo En Chan, Sarah Ryan, Eva Bugallo-Blanco, Pärt Peterson, Kai Kisand, Liis Haljasmägi, Loubna Chadli, Philippe Moingeon, Lauren Martinez, Blair Merrick, Karen Bisnauthsing, Kate Brooks, Mohammad A. A. Ibrahim, Jeremy Mason, Federico Lopez Gomez, Kola Babalola, Sultan Abdul-Jawad, John Cason, Christine Mant, Jeffrey Seow, Carl Graham, Katie J. Doores, Francesca Di Rosa, Jonathan Edgeworth, Manu Shankar-Hari, Adrian C. Hayday

Original languageEnglish
Pages (from-to)1623-1635
Number of pages13
JournalNature Medicine
Volume26
Issue number10
DOIs
Published1 Oct 2020

Bibliographical note

Funding Information: We thank patients and blood donors who consented in this study and the medical and research teams at Guy’s and St. Thomas Trust hospitals. We thank F. Shah, Z. Collins, S. Papaioannou, C. Trouillet, S. Cipolat and A. Day for logistics; M. Brown, S. Irshad, M. Malim and S. Neil for support and guidance; the Flow Cytometry core at the NIHR Biomedical Research Centre of Guy’s and St Thomas’ Hospital and King’s College London; R. Ellis, M.T. Barberio, R. Yorke, F. Kyle, S. Acors, K. Steel, O. Hemmings, V. Muñoz and J. Warren for technical support and advice. We thank Google for research credits, Basecamp for free unlimited usage of their platform and volunteers at Crowdfight COVID-19. The work was supported by: a Cancer ImmunoTherapy Accelerator award from CRUK (A.C.H.; IDMDB); a CRUK City of London Major Cancer Centre studentship (M.J.); the Wellcome Trust (A.C.H., P.V., I.Z. and V.S.; 106292/Z/14/Z); the Rosetrees Trust (A.C.H.); King’s Together Seed Fund (A.C.H.); Gamma Delta Therapeutics (R.D., D.D. and S.K.); The John Black Charitable Foundation (A.C.H.); and the Francis Crick Institute (A.C.H., L.M. and F.C.), which receives core funding from Cancer Research UK (FC001093), the MRC (FC001093) and the Wellcome Trust (FC001093); NIHR Clinician Scientist Award CS-2016-16-011 (M.S.H.); the NIHR Biomedical Research Centre for the Infectious Diseases Biobank (J.C. and C.M.) and for support of Infection and Immunity (J.E.; RJ112/N027); EMBO ALTF 198-2018 (M.M.R.); an Irvington Fellowship-Cancer Research Institute (D.M.); National Institute of Academic Anaesthesia BJA-RCOA PhD Fellowship WKR0-2018-0047 (M.F.), NIHR Fellowship (A.D. and Y.W.); Clinical Immunology Research Fund for the King’s College Hospital Charitable Trust (M.A.A.I.); UK MRC (MR/N013700/2) (C.G.); EMBL core funding and the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 730879 (F.G., J.B. and J.M.) and Estonian Research Council grant PRG377 (P.P., K.K. and L.H.). The authors also acknowledge King’s College London, the Francis Crick Institute and the EBI for institutional support. The views expressed are those of the authors and not necessarily those of the UK NHS, the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

King's Authors

Abstract

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454