Author:
Potts Martin,Fletcher-Etherington Alice,Nightingale Katie,Mescia Federica,Bergamaschi Laura,Calero-Nieto Fernando J.,Antrobus Robin,Williamson James,Kingston Nathalie,Göttgens Berthold,Bradley John R,Lehner Paul J,Matheson Nicholas J,Smith Kenneth G.C.,Wills Mark R,Lyons Paul A,Weekes Michael P,
Abstract
SummaryCertain 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.
Publisher
Cold Spring Harbor Laboratory