Recovery after COVID-19 and persisting endothelial cell activation and hypercoagulability-The prospective observational ROADMAP-post COVID-19 study

ABSTRACT

Background: Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Aim(s) To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/ Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. Method(s) The following biomarkers were measured Procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP) I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV- 2 (IgG and IgA) were also measured. Result(s) The median interval between symptom onset and screening for SARS-CoV- 2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusion(s) Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study.