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; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; 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

doi:10.1016/j.celrep.2023.112613

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

Cell Rep. 2023 Jun 27;42(6):112613. doi: 10.1016/j.celrep.2023.112613. Epub 2023 May 29.

Authors

Martin Potts¹, Alice Fletcher-Etherington¹, Katie Nightingale¹, Federica Mescia², Laura Bergamaschi², Fernando J Calero-Nieto³, Robin Antrobus¹, James Williamson²; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Harriet Parsons¹, Edward L Huttlin³, Nathalie Kingston⁴, Berthold Göttgens⁵, John R Bradley⁶, Paul J Lehner², Nicholas J Matheson⁷, Kenneth G C Smith², Mark R Wills², Paul A Lyons², Michael P Weekes⁸

Affiliations

¹ Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
² 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.
³ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
⁴ NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Department of Haematology, University of Cambridge, Cambridge CB2 0AW, UK.
⁵ Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 OAW, UK.
⁶ Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
⁷ 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.
⁸ Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: mpw1001@cam.ac.uk.

Abstract

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.

Keywords: CP: Immunology.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

COVID-19*
Humans
Leukocytes, Mononuclear
Phenotype
Proteomics
SARS-CoV-2

Abstract

Publication types

MeSH terms

Grants and funding