Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Centro Nacional de Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J Appl Physiol (1985). 2023 Oct 1;135(4):950-955. doi: 10.1152/japplphysiol.00424.2023. Epub 2023 Sep 7.
Endothelial dysfunction is a key phenomenon in COVID-19, induced by direct viral endothelial infection and secondary inflammation, mainly affecting the microvascular circulation. However, few studies described the subcellular aspects of the lung microvasculature and the associated thrombotic phenomena, which are widely present in severe COVID-19 cases. To that end, in this transversal observational study we performed transmission and scanning electron microscopy in nine lung samples of patients who died due to COVID-19, obtained via minimally invasive autopsies in Sao Paulo, Brazil, in 2020. All patients died due to acute respiratory failure and had microvascular thrombosis at histology. Electron microscopy revealed areas of endothelial damage with basal lamina disruption and virus infection in endothelial cells. In the capillary lumens, the ultrastructure of the thrombi is depicted, with red blood cells stacking, dysmorphism and hemolysis, fibrin meshworks, and extracellular traps. Our description illustrates the complex pathophysiology of microvascular thrombosis at the cellular level, which leads to some of the peculiar characteristics of severe COVID-19. In this study, electron microscopy was used to explain the pathophysiology of respiratory failure in severe COVID-19. Before the advent of vaccination, as the virus entered the respiratory system, it rapidly progressed to the alveolar capillary network and, before causing exudative alveolar edema, it caused mainly thrombosis of the pulmonary microcirculation with preserved lung compliance explaining "happy hypoxia." Timing of anticoagulation is of pivotal importance in this disease.
内皮功能障碍是 COVID-19 的一个关键现象，由病毒直接感染内皮细胞和继发炎症引起，主要影响微血管循环。然而，很少有研究描述过 COVID-19 中广泛存在的肺部微血管的亚细胞结构及其相关的血栓形成现象。为此，在这项巴西圣保罗 2020 年通过微创尸检获得的 9 例因 COVID-19 死亡患者的肺样本的横断面观察性研究中，我们进行了透射和扫描电子显微镜检查。所有患者均因急性呼吸衰竭死亡，组织学检查显示有微血管血栓形成。电子显微镜显示内皮细胞的内皮损伤区，伴有基底层破坏和病毒感染。在毛细血管腔中，还描绘了血栓的超微结构，表现为红细胞堆积、畸形和溶血、纤维蛋白网和细胞外陷阱。我们的描述说明了细胞水平上微血管血栓形成的复杂病理生理学，这导致了 COVID-19 严重程度的一些特殊特征。在这项研究中，电子显微镜用于解释 COVID-19 导致的呼吸衰竭的病理生理学。在疫苗问世之前，随着病毒进入呼吸系统，它迅速进展到肺泡毛细血管网络，在引起渗出性肺泡水肿之前，它主要引起肺微循环的血栓形成，而肺顺应性保持不变，这解释了“快乐低氧血症”。在这种疾病中，抗凝治疗的时机至关重要。
