Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study

• Published in: Frontiers in immunology Vol. 13; p. 941742
• Main Authors: Bruni, Flavio, Charitos, Panteleimon, Lampart, Maurin, Moser, Stephan, Siegemund, Martin, Bingisser, Roland, Osswald, Stefan, Bassetti, Stefano, Twerenbold, Raphael, Trendelenburg, Marten, Rentsch, Katharina M, Osthoff, Michael
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.09.2022
• Subjects: Biomarkers; complement system; Complement System Proteins; COVID-19; E-Selectin; Endothelial Cells; Female; Galectin 3; Humans; ICAM-1; Immunology; Inflammation; Intercellular Adhesion Molecule-1; Male; Prospective Studies; SARS-CoV-2; Thrombosis; Vascular Cell Adhesion Molecule-1; VCAM-1; COVID-19; SARS-CoV-2; VCAM-1; endothelial cells; complement system; E-Selectin; ICAM-1; galectin-3
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.941742

Thromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection. In a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1. 153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group. Our data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., "over"-activation).