Comparison of Host Endothelial, Epithelial and Inflammatory Response in ICU Patients With and Without COVID-19

Abstract

Rationale: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Objective: To evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19Methods: We prospectively enrolled 169 ICU patients with suspicion of COVID-19 infection, including 78 (46%) patients positive and 91 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 hours and 3 days after ICU admission. Measurement and Main Results: ICU patients with and without COVID-19 had similar rates of severe acute kidney injury, shock, thromboembolism and in-hospital mortality. Rates of ARDS were higher in COVID-19 (aRR = 5.9, 95% CI: 3.2-11.0). While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores (Figure 1). In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (Bonferroni corrected p<0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients.Conclusions: These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction is not characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics. 2 (Table Presented).