Blasco Ana, Coronado María-José, Hernández-Terciado Fernando, Martín Paloma, Royuela Ana, Ramil Elvira, García Diego, Goicolea Javier, Del Trigo María, Ortega Javier, Escudier Juan M, Silva Lorenzo, Bellas Carmen
Cardiology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
Confocal Microscopy Unit, Instituto de Investigación Puerta de Hierro-Segovia de Arana, Madrid, Spain.
JAMA Cardiol. 2021 Apr 1;6(4):469-474. doi: 10.1001/jamacardio.2020.7308.
Severe coronavirus disease 2019 (COVID-19) is characterized by the intense formation of neutrophil extracellular traps (NETs), leading to the occlusion of microvessels, as shown in pulmonary samples. The occurrence of ST-elevated myocardial infarction (STEMI) is a serious cardiac manifestation of COVID-19; the intrinsic mechanism of coronary thrombosis appears to still be unknown.
To determine the role of NETs in coronary thrombosis in patients with COVID-19.
DESIGN, SETTING, AND PARTICIPANTS: This was a consecutive series of patients with COVID-19 at an academic tertiary hospital in Madrid, Spain, who underwent primary coronary interventions for STEMI in which coronary aspirates were obtained in the catheterization laboratory using a thrombus aspiration device. Patients with COVID-19 who experienced a STEMI between March 23 and April 11, 2020, from whom coronary thrombus samples were aspirated during primary coronary intervention, were included in the analysis. These patients were compared with a series conducted from July 2015 to December 2015 of patients with STEMI.
The presence and quantity of NETs in coronary aspirates from patients with STEMI and COVID-19. The method for the analysis of NETs in paraffin-embedded coronary thrombi was based on the use of confocal microscopy technology and image analysis for the colocalization of myeloperoxidase-DNA complexes and citrullinated histone H3. Immunohistochemical analysis of thrombi was also performed. Clinical and angiographic variables were prospectively collected.
Five patients with COVID-19 were included (4 men [80%]; mean [SD] age, 62 [14] years); the comparison group included 50 patients (44 males [88%]; mean [SD] age, 58 [12] years). NETs were detected in the samples of all 5 patients with COVID-19, and the median density of NETs was 61% (95% CI, 43%-91%). In the historical series of patients with STEMI, NETs were found in 34 of 50 thrombi (68%), and the median NET density was 19% (95% CI, 13%-22%; P < .001). All thrombi from patients with COVID-19 were composed of fibrin and polymorphonuclear cells. None of them showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture.
In this small case series of patients with COVID-19 and myocardial infarction, NETs seem to play a major role in the pathogenesis of STEMI in COVID-19 disease. Our findings support the idea that targeting intravascular NETs might be a relevant goal of treatment and a feasible way to prevent coronary thrombosis in patients with severe COVID-19 disease.
2019年冠状病毒病（COVID-19）重症患者的特征是中性粒细胞胞外陷阱（NETs）大量形成，导致微血管堵塞，如肺部样本所示。ST段抬高型心肌梗死（STEMI）的发生是COVID-19严重的心脏表现；冠状动脉血栓形成的内在机制似乎仍不清楚。
确定NETs在COVID-19患者冠状动脉血栓形成中的作用。
设计、地点和参与者：这是西班牙马德里一家学术三级医院中一系列连续的COVID-19患者，他们因STEMI接受了冠状动脉介入治疗，在导管室使用血栓抽吸装置获取冠状动脉吸出物。纳入分析的患者为2020年3月23日至4月11日期间发生STEMI且在冠状动脉介入治疗期间吸出冠状动脉血栓样本的COVID-19患者。将这些患者与2015年7月至2015年12月期间的STEMI患者系列进行比较。
STEMI合并COVID-19患者冠状动脉吸出物中NETs的存在情况和数量。石蜡包埋冠状动脉血栓中NETs的分析方法基于共聚焦显微镜技术和髓过氧化物酶-DNA复合物与瓜氨酸化组蛋白H3共定位的图像分析。还对血栓进行了免疫组织化学分析。前瞻性收集临床和血管造影变量。
纳入5例COVID-19患者（4例男性[80%]；平均[标准差]年龄，62[14]岁）；对照组包括5例患者（44例男性[88%]；平均[标准差]年龄，58[12]岁）。所有5例COVID-19患者的样本中均检测到NETs，NETs的中位密度为61%（95%CI，43%-91%）。在STEMI患者的历史系列中，50个血栓中有34个（68%）发现有NETs，NETs的中位密度为19%（95%CI，13%-22%；P<0.001）。所有COVID-19患者的血栓均由纤维蛋白和多形核细胞组成。没有一个显示动脉粥样硬化斑块碎片或提示既往斑块破裂的铁沉积。
在这个COVID-19合并心肌梗死的小病例系列中，NETs似乎在COVID-19疾病中STEMI的发病机制中起主要作用。我们的研究结果支持这样一种观点，即针对血管内NETs可能是治疗的一个相关目标，也是预防重症COVID-19患者冠状动脉血栓形成的一种可行方法。
