Ultrastructural characterization of alveolar microvascular damage in severe COVID-19 respiratory failure

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.