Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study
Grigorios T. Gerotziafas,
Patrick Van Dreden,
Theodoros N. Sergentanis,
Marianna Politou,
Aurélie Rousseau,
Matthieu Grusse,
Michèle Sabbah,
Ismail Elalamy,
Vasiliki Pappa,
Tina Skourti,
Tina Bagratuni,
Ioannis Ntanasis-Stathopoulos,
Eleni Korompoki,
Stavroula Labropoulou,
Meletios A. Dimopoulos,
Evangelos Terpos
Affiliations
Grigorios T. Gerotziafas
Sorbonne Université, INSERM UMR_S938, Research Group «Cancer-Hemostasis-Angiogenesis», Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, 75013 Paris, France
Patrick Van Dreden
Sorbonne Université, INSERM UMR_S938, Research Group «Cancer-Hemostasis-Angiogenesis», Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, 75013 Paris, France
Theodoros N. Sergentanis
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Marianna Politou
Hematology Laboratory—Blood Bank, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Aurélie Rousseau
Sorbonne Université, INSERM UMR_S938, Research Group «Cancer-Hemostasis-Angiogenesis», Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, 75013 Paris, France
Matthieu Grusse
Clinical Research Department, Diagnostica Stago, 92036 Gennevilliers, France
Michèle Sabbah
Sorbonne Université, INSERM UMR_S938, Research Group «Cancer-Hemostasis-Angiogenesis», Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, 75013 Paris, France
Ismail Elalamy
Sorbonne Université, INSERM UMR_S938, Research Group «Cancer-Hemostasis-Angiogenesis», Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, 75013 Paris, France
Vasiliki Pappa
Hematology Unit, Second Propaedeutic Department of Internal Medicine and Research Institute, School of Medicine, National and Kapodistrian University of Athens, University General Hospital “Attikon”, 35611 Athens, Greece
Tina Skourti
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Tina Bagratuni
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Ioannis Ntanasis-Stathopoulos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Eleni Korompoki
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Stavroula Labropoulou
National Influenza Reference Laboratory of Southern Greece, Hellenic Pasteur Institute, 35611 Athens, Greece
Meletios A. Dimopoulos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
Evangelos Terpos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 35611 Athens, Greece
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. Objectives. 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. 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. Results. 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. Conclusions. 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.
