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

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; 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

doi:10.1038/s41591-020-1038-6

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

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 CanoMaria 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

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	1623-1635
Number of pages	13
Journal	Nature Medicine
Volume	26
Issue number	10
DOIs	https://doi.org/10.1038/s41591-020-1038-6 https://doi.org/10.1038/s41591-020-1038-6
Publication status	Published - 1 Oct 2020

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Laing, A. G., Lorenc, A., del Molino del Barrio, I., Das, A., Fish, M., Monin, L., Muñoz-Ruiz, M., McKenzie, D. R., Hayday, T. S., Francos-Quijorna, I., Kamdar, S., Joseph, M., Davies, D., Davis, R., Jennings, A., Zlatareva, I., Vantourout, P., Wu, Y., Sofra, V., ... Hayday, A. C. (2020). A dynamic COVID-19 immune signature includes associations with poor prognosis. Nature Medicine, 26(10), 1623-1635. https://doi.org/10.1038/s41591-020-1038-6, https://doi.org/10.1038/s41591-020-1038-6

@article{e3848cf61a074e75ba0107847c895a4b,

title = "A dynamic COVID-19 immune signature includes associations with poor prognosis",

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.",

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

note = "Funding Information: We thank patients and blood donors who consented in this study and the medical and research teams at Guy{\textquoteright}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{\textquoteright}s and St Thomas{\textquoteright} Hospital and King{\textquoteright}s College London; R. Ellis, M.T. Barberio, R. Yorke, F. Kyle, S. Acors, K. Steel, O. Hemmings, V. Mu{\~n}oz 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{\textquoteright}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{\textquoteright}s College Hospital Charitable Trust (M.A.A.I.); UK MRC (MR/N013700/2) (C.G.); EMBL core funding and the European Union{\textquoteright}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{\textquoteright}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: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = oct,

day = "1",

doi = "10.1038/s41591-020-1038-6",

language = "English",

volume = "26",

pages = "1623--1635",

journal = "Nature Medicine",

issn = "1546-170X",

publisher = "Nature Publishing Group",

number = "10",

}

Laing, AG , Lorenc, A, del Molino del Barrio, I, Das, A, Fish, M, Monin, L, Muñoz-Ruiz, M, McKenzie, DR, Hayday, TS , Francos-Quijorna, I , Kamdar, S , Joseph, M , Davies, D, Davis, R, Jennings, A , Zlatareva, I , Vantourout, P , Wu, Y , Sofra, V, Cano, F, Greco, M, Theodoridis, E, Freedman, J, Gee, S , Chan, JNE, Ryan, S, Bugallo-Blanco, E, Peterson, P, Kisand, K, Haljasmägi, L, Chadli, L, Moingeon, P, Martinez, L, Merrick, B, Bisnauthsing, K, Brooks, K , Ibrahim, MAA , Mason, J, Lopez Gomez, F, Babalola, K, Abdul-Jawad, S, Cason, J , Mant, C , Seow, J , Graham, C , Doores, KJ, Di Rosa, F, Edgeworth, J , Shankar-Hari, M & Hayday, AC 2020, 'A dynamic COVID-19 immune signature includes associations with poor prognosis', Nature Medicine, vol. 26, no. 10, pp. 1623-1635. https://doi.org/10.1038/s41591-020-1038-6, https://doi.org/10.1038/s41591-020-1038-6

TY - JOUR

T1 - A dynamic COVID-19 immune signature includes associations with poor prognosis

AU - Laing, Adam G.

AU - Lorenc, Anna

AU - del Molino del Barrio, Irene

AU - Das, Abhishek

AU - Fish, Matthew

AU - Monin, Leticia

AU - Muñoz-Ruiz, Miguel

AU - McKenzie, Duncan R.

AU - Hayday, Thomas S.

AU - Francos-Quijorna, Isaac

AU - Kamdar, Shraddha

AU - Joseph, Magdalene

AU - Davies, Daniel

AU - Davis, Richard

AU - Jennings, Aislinn

AU - Zlatareva, Iva

AU - Vantourout, Pierre

AU - Wu, Yin

AU - Sofra, Vasiliki

AU - Cano, Florencia

AU - Greco, Maria

AU - Theodoridis, Efstathios

AU - Freedman, Joshua

AU - Gee, Sarah

AU - Chan, Julie Nuo En

AU - Ryan, Sarah

AU - Bugallo-Blanco, Eva

AU - Peterson, Pärt

AU - Kisand, Kai

AU - Haljasmägi, Liis

AU - Chadli, Loubna

AU - Moingeon, Philippe

AU - Martinez, Lauren

AU - Merrick, Blair

AU - Bisnauthsing, Karen

AU - Brooks, Kate

AU - Ibrahim, Mohammad A. A.

AU - Mason, Jeremy

AU - Lopez Gomez, Federico

AU - Babalola, Kola

AU - Abdul-Jawad, Sultan

AU - Cason, John

AU - Mant, Christine

AU - Seow, Jeffrey

AU - Graham, Carl

AU - Doores, Katie J.

AU - Di Rosa, Francesca

AU - Edgeworth, Jonathan

AU - Shankar-Hari, Manu

AU - Hayday, Adrian C.

N1 - 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.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85089549921&partnerID=8YFLogxK

U2 - 10.1038/s41591-020-1038-6

DO - 10.1038/s41591-020-1038-6

M3 - Article

C2 - 32807934

SN - 1546-170X

VL - 26

SP - 1623

EP - 1635

JO - Nature Medicine

JF - Nature Medicine

IS - 10

ER -

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

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