Objectives 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. Methods 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. Results 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]; p < 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]; p < 0.001), and were significantly lower in patients with nonsevere disease compared with those with severe disease. Conclusion EV and citrullinated histone H3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease.

中文翻译：

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2019 年冠状病毒病患者的细胞外囊泡和瓜氨酸组蛋白 H3

目的 肺血栓形成是 2019 年冠状病毒病 (COVID-19) 的标志。已经描述了最终导致血栓炎症的失调的免疫反应，但病理机制仍不清楚。方法 我们研究了 41 名成人 COVID-19 患者的逆转录酶聚合酶链反应检测结果为阳性，以及 37 名性别和年龄匹配的健康对照。通过流式细胞术和免疫测定法测定血浆中细胞外囊泡 (EV) 和瓜氨酸化组蛋白 H3 水平的数量和表面特征。结果总共有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 [第 25、75 个百分位]）显着高于对照组（658.8 [353.2, 876.6] vs. 435.5 [332.5, 585.3]，几何平均比 [95% 置信区间]：2.6 [1.9 , 3.6]; p < 0.001)。与对照组相比，患者表现出的源自血小板、内皮细胞、白细胞或中性粒细胞的 EV 数量显着增加。来自肺泡巨噬细胞和肺泡上皮细胞的 EV 在血浆中可检测到，并且在患者中显着更高。患者的细胞间粘附分子 1 阳性 EV 水平较高，而两组间组织因子阳性和血管紧张素转换酶阳性 EV 之间没有差异。重症和非重症 COVID-19 患者的 EV 水平没有差异。患者的瓜氨酸组蛋白 H3 水平（ng/mL，中位数 [第 25、第 75 个百分位]）高于对照组（1.42 [0.6, 3.4] vs. 0.31 [0.1, 0.6]，几何平均比：4.44 [2.6, 7.7] ; p < 0.001), 与重症患者相比，非重症患者的发病率显着降低。结论 EV 和瓜氨酸组蛋白 H3 与 COVID-19 相关，可以提供有关该疾病病理生理学的信息。