Abstract
Severe 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. We hypothesized that plasma proteomics may uncover protein biomarkers correlated with COVID-19 ARDS severity. We analyzed the plasma proteome from 32 patients with ARDS and COVID-19 using an aptamer-based platform of 7289 proteins, and correlated protein measurements with sequential organ failure assessment (SOFA) scores at days 1 and 7 of ICU admission. We identified 184 differentially abundant proteins correlated with SOFA at day 1 and 46 proteins at day 7. In a longitudinal analysis, we correlated dynamic changes in protein abundance and SOFA between days 1 and 7 and identified 40 significant proteins. Pathway analysis of significant proteins identified increased ephrin signaling and acute phase response signaling correlated with increased SOFA scores between days 1 and 7, while pathways related to pulmonary fibrosis signaling and wound healing had a negative correlation. These findings suggest that persistent inflammation may drive disease severity, while repair processes correlate with improvements in organ dysfunction. This approach is generalizable to future ARDS cohorts for identification of biomarkers and disease mechanisms as we strive towards targeted therapies in ARDS.