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

Published: 29 March 2023| Version 1 | DOI: 10.17632/dx69469n8x.1
Contributor:
Michael Weekes

Description

Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, 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+CD177+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.

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Institutions

University of Cambridge

Categories

Expression Proteomics

Funding

Medical Research Council

MR/W025647/1

Medical Research Council

2020 R10.6

Wellcome Trust

200871/Z/16/Z

Medical Research Council

MR/L019027

Medical Research Council

MR/N013433/1

Medical Research Council

MR/S036113/1

Cancer Research UK

C1163/A21762

Medical Research Council

MR/S000081X/1

Wellcome Trust

WT/204870/Z/16/Z

Medical Research Council

MR/T032413/1

Wellcome Trust

204845/Z/16/Z

Licence