Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Section for Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
Thromb Haemost. 2022 Jan;122(1):113-122. doi: 10.1055/a-1522-4131. Epub 2021 Jul 11.
Pulmonary thrombus formation is a hallmark of coronavirus disease 2019 (COVID-19). A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear.
We studied 41 adult COVID-19 patients with positive results on reverse-transcriptase polymerase-chain-reaction assays and 37 sex- and age-matched healthy controls. Number and surface characteristics of extracellular vesicles (EVs) and citrullinated histone H3 levels were determined in plasma upon inclusion by flow cytometry and immunoassay.
In total, 20 patients had severe and 21 nonsevere disease. The number of EV (median [25th, 75th percentile]) was significantly higher in patients compared with controls (658.8 [353.2, 876.6] vs. 435.5 [332.5, 585.3], geometric mean ratio [95% confidence intervals]: 2.6 [1.9, 3.6]; < 0.001). Patients exhibited significantly higher numbers of EVs derived from platelets, endothelial cells, leukocytes, or neutrophils than controls. EVs from alveolar-macrophages and alveolar-epithelial cells were detectable in plasma and were significantly higher in patients. Intercellular adhesion molecule-1-positive EV levels were higher in patients, while no difference between tissue factor-positive and angiotensin-converting enzyme-positive EV was seen between both groups. Levels of EV did not differ between patients with severe and nonsevere COVID-19. Citrullinated histone H3 levels (ng/mL, median [25th, 75th percentile]) were higher in patients than in controls (1.42 [0.6, 3.4] vs. 0.31 [0.1, 0.6], geometric mean ratio: 4.44 [2.6, 7.7]; < 0.001), and were significantly lower in patients with nonsevere disease compared with those with severe disease.
EV and citrullinated histone H3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease.
肺血栓形成是 2019 年冠状病毒病（COVID-19）的一个标志。现已描述了最终导致血栓炎症的失调免疫反应，但发病机制尚不清楚。
我们研究了 41 名经逆转录酶聚合酶链反应检测呈阳性的成年 COVID-19 患者和 37 名性别和年龄匹配的健康对照者。通过流式细胞术和免疫测定法在纳入时确定血浆中外泌体（EV）的数量和表面特征以及瓜氨酸化组蛋白 H3 水平。
总共 20 名患者患有严重疾病，21 名患者患有非严重疾病。与对照组相比，患者的 EV 数量（中位数[25%，75%]）明显更高（658.8 [353.2，876.6]与 435.5 [332.5，585.3]，几何均数比[95%置信区间]：2.6 [1.9，3.6]； < 0.001）。患者的血小板、内皮细胞、白细胞或中性粒细胞来源的 EV 数量明显高于对照组。肺泡巨噬细胞和肺泡上皮细胞来源的 EV 可在血浆中检测到，且在患者中明显升高。细胞间黏附分子 1 阳性 EV 水平在患者中较高，而两组之间组织因子阳性和血管紧张素转换酶阳性 EV 之间未见差异。严重和非严重 COVID-19 患者之间的 EV 水平无差异。瓜氨酸化组蛋白 H3 水平（ng/mL，中位数[25%，75%]）在患者中高于对照组（1.42 [0.6，3.4]与 0.31 [0.1，0.6]，几何均数比：4.44 [2.6，7.7]； < 0.001），而非严重疾病患者的水平明显低于严重疾病患者。
EV 和瓜氨酸化组蛋白 H3 与 COVID-19 相关，可提供有关疾病病理生理学的信息。
