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 D 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 D 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

Abstract / Description of output

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
Publication status	Published - 17 Aug 2020

Keywords / Materials (for Non-textual outputs)

Aged
Antibodies, Viral/immunology
B-Lymphocyte Subsets/immunology
B-Lymphocytes/immunology
Basophils/immunology
Betacoronavirus
COVID-19
Case-Control Studies
Cell Cycle
Chemokine CXCL10/immunology
Chemokines/immunology
Cohort Studies
Coronavirus Infections/blood
Cytokines/immunology
Dendritic Cells/immunology
Disease Progression
Female
Flow Cytometry
Hospitalization
Humans
Immunologic Memory
Immunophenotyping
Interleukin-10/immunology
Interleukin-6/immunology
Leukocyte Count
Lymphocyte Activation/immunology
Male
Middle Aged
Pandemics
Pneumonia, Viral/blood
Prognosis
SARS-CoV-2
Severity of Illness Index
T-Lymphocyte Subsets/immunology
T-Lymphocytes/immunology
Up-Regulation

Access to Document

10.1038/s41591-020-1038-6

Cite this

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

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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.",

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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 Freedman, {Joshua D} 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}",

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

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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, JD, 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

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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 D

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

PY - 2020/8/17

Y1 - 2020/8/17

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.

KW - Aged

KW - Antibodies, Viral/immunology

KW - B-Lymphocyte Subsets/immunology

KW - B-Lymphocytes/immunology

KW - Basophils/immunology

KW - Betacoronavirus

KW - COVID-19

KW - Case-Control Studies

KW - Cell Cycle

KW - Chemokine CXCL10/immunology

KW - Chemokines/immunology

KW - Cohort Studies

KW - Coronavirus Infections/blood

KW - Cytokines/immunology

KW - Dendritic Cells/immunology

KW - Disease Progression

KW - Female

KW - Flow Cytometry

KW - Hospitalization

KW - Humans

KW - Immunologic Memory

KW - Immunophenotyping

KW - Interleukin-10/immunology

KW - Interleukin-6/immunology

KW - Leukocyte Count

KW - Lymphocyte Activation/immunology

KW - Male

KW - Middle Aged

KW - Pandemics

KW - Pneumonia, Viral/blood

KW - Prognosis

KW - SARS-CoV-2

KW - Severity of Illness Index

KW - T-Lymphocyte Subsets/immunology

KW - T-Lymphocytes/immunology

KW - Up-Regulation

U2 - 10.1038/s41591-020-1038-6

DO - 10.1038/s41591-020-1038-6

M3 - Article

C2 - 32807934

SN - 1078-8956

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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