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Cell Rep
. 2023 May 29;42(6):112613.
doi: 10.1016/j.celrep.2023.112613. Online ahead of print. Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity
Martin Potts 1 , Alice Fletcher-Etherington 1 , Katie Nightingale 1 , Federica Mescia 2 , Laura Bergamaschi 2 , Fernando J Calero-Nieto 3 , Robin Antrobus 1 , James Williamson 2 ; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Harriet Parsons 1 , Edward L Huttlin 3 , Nathalie Kingston 4 , Berthold Göttgens 5 , John R Bradley 6 , Paul J Lehner 2 , Nicholas J Matheson 7 , Kenneth G C Smith 2 , Mark R Wills 2 , Paul A Lyons 2 , Michael P Weekes 8
Affiliations
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.
. 2023 May 29;42(6):112613.
doi: 10.1016/j.celrep.2023.112613. Online ahead of print. Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity
Martin Potts 1 , Alice Fletcher-Etherington 1 , Katie Nightingale 1 , Federica Mescia 2 , Laura Bergamaschi 2 , Fernando J Calero-Nieto 3 , Robin Antrobus 1 , James Williamson 2 ; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Harriet Parsons 1 , Edward L Huttlin 3 , Nathalie Kingston 4 , Berthold Göttgens 5 , John R Bradley 6 , Paul J Lehner 2 , Nicholas J Matheson 7 , Kenneth G C Smith 2 , Mark R Wills 2 , Paul A Lyons 2 , Michael P Weekes 8
Affiliations
- PMID: 37302069
- DOI: 10.1016/j.celrep.2023.112613
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.