Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Grigorios T Gerotziafas,Vasiliki Pappa,Patrick Van Dreden,Meletios A Dimopoulos,Aurélie Rousseau,Eleni Korompoki,Michèle Sabbah,Theodoros N Sergentanis,Stavroula Labropoulou,Ismail Elalamy,Evangelos Terpos,Marianna Politou,Tina Bagratuni,Matthieu Grusse,Tina Skourti,Ioannis Ntanasis-Stathopoulos

doi:10.3390/hemato3010010

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. 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.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which led to death more than 5.6 million patients worldwide.In patients with severe COVID-19, activation of blood coagulation and endothelial cells orchestrated with complement activation and cytokine storm leads to disease worsening and death [1].Hypercoagulable state and endothelial cell activation and fibrinolytic unbalance are common alterations in patients with COVID-19 hospitalized either at the conventional medical ward or at the intensive care unit (ICU) [2,3]
The ROADMAP-postCOVID-19 study included COVID-19 survivors who participated in the phase II study (NCT04408209) for the assessment of efficacy and safety of convalescent plasma treatment of COVID-19 infection started in Greece on 28 April 2020
It is well established that in patients with COVID-19, endothelial cell activation and hypercoagulability are independently associated with the risk of disease worsening, admission in ICU and intubation, as well as with high mortality rate [22]

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which led to death more than 5.6 million patients worldwide.In patients with severe COVID-19, activation of blood coagulation and endothelial cells orchestrated with complement activation and cytokine storm leads to disease worsening and death [1].Hypercoagulable state and endothelial cell activation and fibrinolytic unbalance are common alterations in patients with COVID-19 hospitalized either at the conventional medical ward or at the intensive care unit (ICU) [2,3]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which led to death more than 5.6 million patients worldwide. In patients with severe COVID-19, activation of blood coagulation and endothelial cells orchestrated with complement activation and cytokine storm leads to disease worsening and death [1]. There are limited data in small series of patient, on the persistence of hypercoagulability and endothelial cell activation following recovery from COVID-19. The answer to this question is required to proceed to the research of biomarkers mandatory for the risk of either vascular complications after recovery from

Methods

Results

Conclusion