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 C. Williamson, Harriet T. 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 Lyons, Michael P. Weekes
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.