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.
【저자키워드】 Inflammation, Microvesicles, SARS–CoV–2, hypercoaguability, venous thomboembolism, 【초록키워드】 ACE2, thrombosis, Symptom, discharge, flow cytometry, Coagulopathy, Clinical outcome, sensitivity, male, Patient, Platelet, pericyte, age, extracellular vesicle, Admission, association, Angiotensin-converting enzyme, Concentration, Analysis, COVID-19 patient, plasma concentration, tissue, acute phase, blood sample, growth factor, unit, CD45, cellular activation, EVs, Cell, CD45+, analyzed, collected, significantly, involved, recruited, evaluated, activated, expressing, baseline, persist, PPL, 【제목키워드】 COVID-19, trend, longitudinal,