Longitudinal Trend of Plasma Concentrations of Extracellular Vesicles in Patients Hospitalized for COVID-19.
Longitudinal Trend of Plasma Concentrations of Extracellular Vesicles in Patients Hospitalized for COVID-19.
复制标题
DOI：
10.3389/fcell.2021.770463
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Simioni P
中科院分区：
文献类型：
--
作者：
Campello E;Radu CM;Simion C;Spiezia L;Bulato C;Gavasso S;Tormene D;Perin N;Turatti G;Simioni P
本研究评估了covid -19相关凝血病（CAC）相关细胞的细胞外囊泡（EVs）血浆浓度、纵向趋势及其与临床结果的相关性。在入院48小时、出院时和出院后30天内，对某医疗单位连续入院的COVID-19患者进行纵向采集血液样本。采用高灵敏度流式细胞术和磷脂依赖凝血时间（PPL）对EVs进行分析。检测内皮、血小板、白细胞源性、承载组织因子(TF)+、血管紧张素转换酶(ACE2)+、血小板源性生长因子受体-β (PDGF-β)+、sars - cov -2核蛋白(NP)+。91例患者纳入基线EV分析（平均年龄67±14岁，50.5%为男性），48例进行纵向评估。从基线到出院后30天，我们观察到血浆中内皮源性ev （e-选择素+）、内皮源性ev （e-选择素+TF+）、内皮源性ev （e-选择素+ACE2+）和白细胞源性ev （CD45+TF+）的浓度分别显著降低，p < 0.001, p = 0.03, p = 0.001, p = 0.001。相反，血小板来源的（p -选择素+）和白细胞来源的EVs （CD45+）从基线到出院后30天增加（p分别= 0.038和0.032）。EVs TF+、ACE2+、PDGF-β+和SARS-CoV-2-NP+在监测期间无显著变化。PPL从基线到出院后30天增加（+ 6.3 s, p = 0.006）。p -选择素+ EVs≤1054 /µL与血栓形成相关（p = 0.024）， e -选择素+ EVs≤531/µL与恶化/死亡相关（p 0.026）， 30天p -选择素+和CD45 + EVs与持续症状相关（p < 0.0001）。我们证实，入院和出院时，来自CAC相关细胞的ev增加。还检测到来自活化周细胞并表达SARS-CoV-2-NP的ev。出院后30天，内皮- ev减少，而血小板和白细胞- ev进一步增加，表明细胞活化在急性期后仍持续很长时间。
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.