Plasma proteomics and organ dysfunction in COVID-19 ARDS

Fatal COVID-19 is often complicated by hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). Mechanisms governing lung injury and repair in ARDS remain poorly understood because there are no biomarker-targeted therapeutics for patients with ARDS. We hypothesized that plasma proteomics may uncover unique biomarkers that correlate with disease severity in COVID-19 ARDS. We analyzed the circulating plasma proteome from 32 patients with ARDS and COVID-19 using an aptamer-based platform, which measures 7289 proteins, and correlated protein measurements with sequential organ failure assessment (SOFA) scores at 2 time points (Days 1 and 7 following ICU admission). We compared differential protein abundance and SOFA scores at each individual time point and identified 119 proteins at Day 1 and 46 proteins at Day 7 that correlated with patient SOFA scores. We modeled the relationship between dynamic protein abundance and changes in SOFA score between Days 1 and 7 and identified 39 proteins that significantly correlated with changes in SOFA score. Using Ingenuity Pathway Analysis, we identified increased ephrin signaling and acute phase response signaling correlated with increased SOFA scores over time, while pathways related to pulmonary fibrosis signaling and wound healing had an inverse relationship with SOFA scores between Days 1 and 7. These findings suggest that persistent inflammation may drive worsened disease severity, while repair processes correlate with improvements in organ dysfunction over time. This approach is generalizable to more diverse ARDS cohorts for identification of protein biomarkers and disease mechanisms as we strive towards targeted therapies in ARDS. Proteomic profiles via SomaLogic aptamer-based microarray (SomaScan 7k v.4) from plasma from ARDS patients with COVID-19 with variable degrees of organ dysfunction.