Abstract
Plasma concentrations of extracellular vesicles (EVs) originating from cells involved in COVID-19-associated coagulopathy (CAC), their longitudinal trend and association with clinical outcomes were evaluated. Blood samples of consecutive COVID-19 patients admitted to a medical Unit were longitudinally collected within 48 h of admission, at discharge and 30 days post-discharge. EVs were analyzed using high sensitivity flow cytometry and phospholipid-dependent clotting time (PPL). The following EVs were measured: endothelium-, platelet-, leukocyte-derived, bearing tissue factor (TF)+, angiotensin-converting enzyme (ACE2)+, platelet-derived growth factor receptor-β (PDGF-β)+ and SARS-CoV-2-nucleoprotein (NP)+. 91 patients were recruited for baseline EV analysis (mean age 67 ± 14 years, 50.5% male) and 48 underwent the longitudinal evaluation. From baseline to 30-days post-discharge, we observed significantly decreased plasma concentrations of endothelium-derived EVs (E-Selectin+), endothelium-derived bearing TF (E-Selectin+ TF+), endothelium-derived bearing ACE2 (E-Selectin+ACE2+) and leukocyte-EVs bearing TF (CD45+TF+), p < 0.001, p = 0.03, p = 0.001, p = 0.001, respectively. Conversely, platelet-derived (P-Selectin+) and leukocyte-derived EVs (CD45+) increased from baseline to 30-days post-discharge (p = 0.038 and 0.032, respectively). EVs TF+, ACE2+, PDGF-β+, and SARS-CoV-2-NP+ did not significantly change during the monitoring. PPL increased from baseline to 30-days post-discharge (+ 6.3 s, p = 0.006). P-Selectin + EVs >1,054/µL were associated with thrombosis (p = 0.024), E-Selectin + EVs ≤531/µL with worsening/death (p 0.026) and 30-days P-Selectin+ and CD45 + EVs with persistent symptoms (p < 0.0001). We confirmed increased EVs originating from cells involved in CAC at admission and discharge. EVs derived from activated pericytes and expressing SARS-CoV-2-NP were also detected. 30-days post-discharge, endothelium-EVs decreased, while platelet- and leukocyte-EVs further increased, indicating that cellular activation persists long after the acute phase.
Highlights
A hypercoagulable state is commonly considered a major component of the pathophysiology of the infectious disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Iba et al, 2020a; Connors and Levy, 2020; Görlinger et al, 2020)
The goals of this study were (a) to confirm plasma concentrations of different extracellular vesicles (EVs) subtypes originating from activated endothelial cells, platelets, leukocytes, pericytes, tissue factor (TF)-bearing, and nucleoprotein (NP) SARS-CoV-2-bearing, as well as EV-associated procoagulant activity in patients hospitalized for COVID-19, and (b) evaluate the longitudinal trend of EV subtypes at discharge and 30 days post-discharge
One hundred and one patients were excluded for the following reasons: 54 for admission from a Department other than Emergency Department (ED); 3 for recent surgery; 7 for admission for acute venous thromboembolism (VTE); 5 for acute renal or liver failure; 20 for ongoing anticoagulant therapy; 12 for transfer to the intensive care unit (ICU) before venous sample collection
Summary
A hypercoagulable state is commonly considered a major component of the pathophysiology of the infectious disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Iba et al, 2020a; Connors and Levy, 2020; Görlinger et al, 2020). Measuring the plasma concentrations of one specific MV could potentially provide diagnostic and prognostic information about silent conditions (Owens and Mackman, 2011; Mooberry and Key, 2016; van der Pol et al, 2016; Campello et al, 2016b). COVID-19 patients show many of the pathophysiological processes that are associated with the cellular release of EVs, including endothelial injury, platelet hyper-reactivity, TF-mediated procoagulant activity, and increased thrombin generation (Iba et al, 2020b; Spiezia et al, 2020; Campello et al, 2021a; Lippi et al, 2021). It was showed that COVID-19 patients exhibited significantly higher numbers of EVs derived from platelets, endothelial cells, leukocytes, or neutrophils than controls (Traby et al, 2021). There is currently no data on the trend of EV levels after COVID-19 remission
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