Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity

Martin Potts; Alice Fletcher-Etherington; Katie Nightingale; Federica Mescia; Laura Bergamaschi; Fernando J. Calero-Nieto; Robin Antrobus; James Williamson; Harriet Parsons; Edward L. Huttlin; Nathalie Kingston; Berthold Göttgens; John R. Bradley; Paul J. Lehner; Nicholas J. Matheson; Kenneth G.C. Smith; Mark R. Wills; Paul A. Lyons; Michael P. Weekes

Cell Reports (Jun 2023)

Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity

Martin Potts,
Alice Fletcher-Etherington,
Katie Nightingale,
Federica Mescia,
Laura Bergamaschi,
Fernando J. Calero-Nieto,
Robin Antrobus,
James Williamson,
Harriet Parsons,
Edward L. Huttlin,
Nathalie Kingston,
Berthold Göttgens,
John R. Bradley,
Paul J. Lehner,
Nicholas J. Matheson,
Kenneth G.C. Smith,
Mark R. Wills,
Paul A. Lyons,
Michael P. Weekes

Affiliations

Martin Potts: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
Alice Fletcher-Etherington: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
Katie Nightingale: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
Federica Mescia: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Laura Bergamaschi: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Fernando J. Calero-Nieto: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Robin Antrobus: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
James Williamson: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Harriet Parsons: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
Edward L. Huttlin: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Nathalie Kingston: NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK
Berthold Göttgens: Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 OAW, UK
John R. Bradley: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK
Paul J. Lehner: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Nicholas J. Matheson: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; NHS Blood and Transplant, Cambridge CB2 0PT, UK
Kenneth G.C. Smith: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Mark R. Wills: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Paul A. Lyons: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK
Michael P. Weekes: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Corresponding author

Journal volume & issue: Vol. 42, no. 6
p. 112613

Abstract

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Summary: Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. The cell-surface proteins CEACAMs1, 6, and 8, CD177, CD63, and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CEACAM1/6/8+CD177+CD63+CD89+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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