Plasma biomarkers of immunothrombosis are independently associated with death in patients with COVID-19 on ECMO.

Abstract

Critical illness in COVID-19 may require support with Extracorporeal Membrane Oxygenation (ECMO). As immunothrombosis contributes to pathogenesis of critical illness we quantified immunothrombotic markers in patients with COVID-19 on ECMO and evaluated the predictive capacity of these markers for death. We performed a retrospective analysis of 74 consecutive patients with COVID-19 on ECMO at a single academic medical center between March 2020 and February 2021. SARS-CoV-2 nucleocapsid RNA and 16 immunothrombotic biomarkers were longitudinally quantified. Biomarker trajectories were assessed with univariate and multivariate models and used to predict death and decannulation across multiple models. Male sex, smoking status, high serum bilirubin level, and low partial pressure of oxygen in arterial blood to the fraction of inspired oxygen (P/F) ratio were associated with an increased risk of death. Plasma levels of 10 immunothrombotic markers were significantly elevated in fatal cases. Elevated IL-8 and von Willebrand factor (VWF) were associated with an increased hazard of death and elevated angiopoietin-2, IL-1β, IL-6, IL-8, IL-18, ICAM, p-selectin, syndecan-1, and VWF were associated with a decreased hazard for decannulation when adjusting for sex, smoking status, and time to cannulation. Predictive models incorporating biomarkers were superior to demographics alone and equivalent to models including clinical information. We found increased immunothrombotic markers, male sex, and history of smoking were risk factors in patients with COVID-19 on ECMO who died as compared to those who were decannulated. These findings are important for understanding the pathogenesis of severe COVID-19 and prognostication.