Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging

We examine the cellular and soluble determinants of coronavirus disease 2019 (COVID-19) relative to aging by performing mass cytometry in parallel with clinical blood testing and plasma proteomic profiling of ~4,700 proteins from 71 individuals with pulmonary disease and 148 healthy donors (25–80 years old). Distinct cell populations were associated with age (GZMK+CD8+ T cells and CD25low CD4+ T cells) and with COVID-19 (TBET−EOMES− CD4+ T cells, HLA-DR+CD38+ CD8+ T cells and CD27+CD38+ B cells). A unique population of TBET+EOMES+ CD4+ T cells was associated with individuals with COVID-19 who experienced moderate, rather than severe or lethal, disease. Disease severity correlated with blood creatinine and urea nitrogen levels. Proteomics revealed a major impact of age on the disease-associated plasma signatures and highlighted the divergent contribution of hepatocyte and muscle secretomes to COVID-19 plasma proteins. Aging plasma was enriched in matrisome proteins and heart/aorta smooth muscle cell-specific proteins. These findings reveal age-specific and disease-specific changes associated with COVID-19, and potential soluble mediators of the physiological impact of COVID-19. Arthur et al. report the biochemical and proteomic (SomaLogic) profiling of plasma and CyTOF immunophenotyping of peripheral blood mononuclear cells from 71 individuals with COVID-19 or other inflammatory pulmonary diseases, and 148 healthy donors aged 25–80 years old. The Resource reveals unique determinants of COVID-19 disease relative to healthy aging and other pulmonary disorders.