Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

Elizabeth R. Mann; Madhvi Menon; Sean Blandin Knight; Joanne E. Konkel; Christopher Jagger; Tovah N. Shaw; Siddharth Krishnan; Magnus Rattray; Andrew Ustianowski; Nawar Diar Bakerly; Paul Dark; Graham Lord; Angela Simpson; Timothy Felton; Ling-Pei Ho; Marc Feldmann; John R. Grainger; Tracy Hussell; Nicholas Scott; Alexander Mathioudakis

doi:10.1126/sciimmunol.abd6197

Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

Elizabeth R. Mann, Madhvi Menon, Sean Blandin Knight, Joanne E. Konkel, Christopher Jagger, Tovah N. Shaw, Siddharth Krishnan, Magnus Rattray, Andrew Ustianowski, Nawar Diar Bakerly, Paul Dark, Graham Lord, Angela Simpson, Timothy Felton, Ling-Pei Ho, Marc Feldmann, John R. Grainger, Tracy Hussell, Nicholas Scott, Alexander Mathioudakis

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

69 Downloads (Pure)

Abstract

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells of hospitalized patients during the peak of the COVID-19 pandemic in the United Kingdom. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1, and IP-10 and modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, and enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of patients with COVID-19 and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission, suggesting that immunomodulating therapies would be most beneficial at early time points.

Original language	English
Article number	eabd6197
Journal	Science Immunology
Volume	5
Issue number	51
DOIs	https://doi.org/10.1126/sciimmunol.abd6197
Publication status	Published - 18 Sept 2020

Keywords

Adult
Aged
Betacoronavirus/immunology
Biomarkers/blood
COVID-19
Coronavirus Infections/blood
Cyclooxygenase 2/immunology
Disease Progression
Female
Host Microbial Interactions/immunology
Humans
Immunity, Innate
Inflammation Mediators/blood
Ki-67 Antigen/immunology
Longitudinal Studies
Male
Middle Aged
Monocytes/immunology
Pandemics
Pneumonia, Viral/blood
Prospective Studies
SARS-CoV-2
Severity of Illness Index
United Kingdom/epidemiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/sciimmunol.abd6197

2020_Mann_CIRCOAccepted author manuscript, 2 MBLicence: CC BY

1 Preprint

Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis
Respiratory TRC, CIRCO, Mann, E. R., Menon, M., Knight, S. B., Konkel, J. E., Jagger, C., Shaw, T. N., Krishnan, S., Rattray, M., Ustianowski, A., Bakerly, N. D., Dark, P., Lord, G., Simpson, A., Felton, T., Ho, L. P., Feldmann, M., Grainger, J. R. & Hussell, T., 1 Jun 2020, medRxiv, 30 p.
Research output: Preprint/Working paper › Preprint

Cite this

Mann, E. R., Menon, M., Knight, S. B., Konkel, J. E., Jagger, C., Shaw, T. N., Krishnan, S., Rattray, M., Ustianowski, A., Bakerly, N. D., Dark, P., Lord, G., Simpson, A., Felton, T., Ho, L.-P., Feldmann, M., Grainger, J. R., Hussell, T., Scott, N., & Mathioudakis, A. (2020). Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19. Science Immunology, 5(51), Article eabd6197. https://doi.org/10.1126/sciimmunol.abd6197

@article{8e5b901de86940f3a705a789eeac22ca,

title = "Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19",

abstract = "COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells of hospitalized patients during the peak of the COVID-19 pandemic in the United Kingdom. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1, and IP-10 and modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, and enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of patients with COVID-19 and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission, suggesting that immunomodulating therapies would be most beneficial at early time points.",

keywords = "Adult, Aged, Betacoronavirus/immunology, Biomarkers/blood, COVID-19, Coronavirus Infections/blood, Cyclooxygenase 2/immunology, Disease Progression, Female, Host Microbial Interactions/immunology, Humans, Immunity, Innate, Inflammation Mediators/blood, Ki-67 Antigen/immunology, Longitudinal Studies, Male, Middle Aged, Monocytes/immunology, Pandemics, Pneumonia, Viral/blood, Prospective Studies, SARS-CoV-2, Severity of Illness Index, United Kingdom/epidemiology",

author = "Mann, {Elizabeth R.} and Madhvi Menon and Knight, {Sean Blandin} and Konkel, {Joanne E.} and Christopher Jagger and Shaw, {Tovah N.} and Siddharth Krishnan and Magnus Rattray and Andrew Ustianowski and Bakerly, {Nawar Diar} and Paul Dark and Graham Lord and Angela Simpson and Timothy Felton and Ling-Pei Ho and Marc Feldmann and Grainger, {John R.} and Tracy Hussell and Nicholas Scott and Alexander Mathioudakis",

note = "Funding Information: Acknowledgments: This report is independent research supported by the North West Lung Centre Charity and National Institute for Health Research Clinical Research Facility at Manchester University NHS Foundation Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the North West Lung Centre Charity, National Institute for Health Research, or the Department of Health. We would like to acknowledge the Manchester Allergy, Respiratory and Thoracic Surgery Biobank, the Northern Care Alliance Research Collection tissue bank, and the North West Lung Centre Charity for supporting this project and thank the study participants for their contribution. A.S., T.F., P.D., and T.H. are supported by the NIHR Manchester Biomedical Research Centre. In addition, we would like to thank the Immunology community within the Lydia Becker Institute of Immunology and Inflammation, the core flow cytometry facility at University of Manchester, the Manchester COVID-19 Rapid Response Group, and the study participants for contribution. Funding: This work was supported by The Kennedy Trust for Rheumatology Research that provided a Rapid Response Award for costs associated with the laboratory analysis of the immune response in patients with COVID-19 to J.R.G., The Wellcome Trust (T.H., 202865/Z/16/Z; 106898/A/15/Z, which helped support some CIRCO members), The Wellcome Trust/Royal Society (E.R.M., 206206/Z/17/Z), the Lister Institute (J.E.K.), and BBSRC (J.E.K., BB/ M025977/1; T.N.S., BB/S01103X/1). The Oxford and Manchester NIHR BRC provided support for study design and sample collection. Funding Information: Acknowledgments: This report is independent research supported by the North West Lung Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",

year = "2020",

month = sep,

day = "18",

doi = "10.1126/sciimmunol.abd6197",

language = "English",

volume = "5",

journal = "Science Immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science (A A A S)",

number = "51",

}

Mann, ER , Menon, M , Knight, SB , Konkel, JE, Jagger, C, Shaw, TN, Krishnan, S, Rattray, M, Ustianowski, A, Bakerly, ND, Dark, P, Lord, G, Simpson, A , Felton, T, Ho, L-P, Feldmann, M, Grainger, JR , Hussell, T , Scott, N & Mathioudakis, A 2020, 'Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19', Science Immunology, vol. 5, no. 51, eabd6197. https://doi.org/10.1126/sciimmunol.abd6197

TY - JOUR

T1 - Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

AU - Mann, Elizabeth R.

AU - Menon, Madhvi

AU - Knight, Sean Blandin

AU - Konkel, Joanne E.

AU - Jagger, Christopher

AU - Shaw, Tovah N.

AU - Krishnan, Siddharth

AU - Rattray, Magnus

AU - Ustianowski, Andrew

AU - Bakerly, Nawar Diar

AU - Dark, Paul

AU - Lord, Graham

AU - Simpson, Angela

AU - Felton, Timothy

AU - Ho, Ling-Pei

AU - Feldmann, Marc

AU - Grainger, John R.

AU - Hussell, Tracy

AU - Scott, Nicholas

AU - Mathioudakis, Alexander

N1 - Funding Information: Acknowledgments: This report is independent research supported by the North West Lung Centre Charity and National Institute for Health Research Clinical Research Facility at Manchester University NHS Foundation Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the North West Lung Centre Charity, National Institute for Health Research, or the Department of Health. We would like to acknowledge the Manchester Allergy, Respiratory and Thoracic Surgery Biobank, the Northern Care Alliance Research Collection tissue bank, and the North West Lung Centre Charity for supporting this project and thank the study participants for their contribution. A.S., T.F., P.D., and T.H. are supported by the NIHR Manchester Biomedical Research Centre. In addition, we would like to thank the Immunology community within the Lydia Becker Institute of Immunology and Inflammation, the core flow cytometry facility at University of Manchester, the Manchester COVID-19 Rapid Response Group, and the study participants for contribution. Funding: This work was supported by The Kennedy Trust for Rheumatology Research that provided a Rapid Response Award for costs associated with the laboratory analysis of the immune response in patients with COVID-19 to J.R.G., The Wellcome Trust (T.H., 202865/Z/16/Z; 106898/A/15/Z, which helped support some CIRCO members), The Wellcome Trust/Royal Society (E.R.M., 206206/Z/17/Z), the Lister Institute (J.E.K.), and BBSRC (J.E.K., BB/ M025977/1; T.N.S., BB/S01103X/1). The Oxford and Manchester NIHR BRC provided support for study design and sample collection. Funding Information: Acknowledgments: This report is independent research supported by the North West Lung Publisher Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

PY - 2020/9/18

Y1 - 2020/9/18

N2 - COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells of hospitalized patients during the peak of the COVID-19 pandemic in the United Kingdom. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1, and IP-10 and modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, and enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of patients with COVID-19 and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission, suggesting that immunomodulating therapies would be most beneficial at early time points.

AB - COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells of hospitalized patients during the peak of the COVID-19 pandemic in the United Kingdom. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1, and IP-10 and modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, and enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of patients with COVID-19 and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission, suggesting that immunomodulating therapies would be most beneficial at early time points.

KW - Adult

KW - Aged

KW - Betacoronavirus/immunology

KW - Biomarkers/blood

KW - COVID-19

KW - Coronavirus Infections/blood

KW - Cyclooxygenase 2/immunology

KW - Disease Progression

KW - Female

KW - Host Microbial Interactions/immunology

KW - Humans

KW - Immunity, Innate

KW - Inflammation Mediators/blood

KW - Ki-67 Antigen/immunology

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Monocytes/immunology

KW - Pandemics

KW - Pneumonia, Viral/blood

KW - Prospective Studies

KW - SARS-CoV-2

KW - Severity of Illness Index

KW - United Kingdom/epidemiology

U2 - 10.1126/sciimmunol.abd6197

DO - 10.1126/sciimmunol.abd6197

M3 - Article

C2 - 32943497

SN - 2470-9468

VL - 5

JO - Science Immunology

JF - Science Immunology

IS - 51

M1 - eabd6197

ER -

Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Research output

Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis

Cite this