Abstract
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.
【초록키워드】 COVID-19, coronavirus disease, aging, severity, B cells, Proteins, Protein, T cell, CD4+ T cells, plasma, age, urea nitrogen, disease, change, moderate, proteomic, CD8+ T cell, CD4+ T cell, Blood, pulmonary disease, cellular, creatinine, Cytometry, physiological, Secretome, determinant, individual, cell population, healthy donor, unique, correlated, disease-associated, individuals with COVID-19, with COVID-19, 【제목키워드】 COVID-19, plasma, proteomic, pulmonary disease, determinant, Non-COVID-19, healthy,