Frontiers in Immunology (Sep 2022)

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

  • Flavio Bruni,
  • Panteleimon Charitos,
  • Maurin Lampart,
  • Stephan Moser,
  • Martin Siegemund,
  • Roland Bingisser,
  • Stefan Osswald,
  • Stefano Bassetti,
  • Raphael Twerenbold,
  • Raphael Twerenbold,
  • Marten Trendelenburg,
  • Katharina M. Rentsch,
  • Michael Osthoff

DOI
https://doi.org/10.3389/fimmu.2022.941742
Journal volume & issue
Vol. 13

Abstract

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BackgroundThromboinflammation 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.MethodsIn 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.Results153 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.ConclusionsOur 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).

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