Unipd Research. Microthrombosis, Severe Liver Disease, and Fatal COVID-19
05.07.2024
The interdisciplinary study Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19 published in the Journal of Hepatology includes those from the University of Padua. The collaborative work brought together researchers from the universities of Yale (USA) and Birmingham (UK), Papa Giovanni XXIII (Bergamo), ASST Bergamo Est Seriate, and Fatebenefratelli Sacco (Milan). The study used a large series of autopsy materials to shed light on the mechanisms of microthrombosis and the relevance of liver pathology in lethal forms of Covid-19.
Prof Luca Fabris of the Department of Medicine of the University of Padua and the Liver Center of Yale University, as well as the corresponding author, explains, “Within the lungs of those with microthorrhbosis in the portal vein, we observed dilations of the intrapulmonary arterial bed that worsened their oxygenation resulting in aggravated lethal respiratory failure.”
Prof Paolo Simioni, Director of the Department of Medicine of the University of Padua and of the 1st Medical Clinic of the Hospital/University of Padua, co-senior author of the study continues, “At the cellular level, our study demonstrated that portal vein microthrombosis is supported by a pro-coagulant response induced by SARS-CoV-2 infection that affects a still very neglected vascular cell type, called pericyte, located at the outside the vessel, where it forms a sheath around the endothelium, the layer of cells that is in direct contact with the blood flow. This type of cell, once infected, activates the vascular secretion of coagulation mediators, including tissue factor and von Willebrand factor, responsible on the one hand for the state of local hypercoagulability with consequent thrombosis, and on the other for the dilation of the small pulmonary arteries resulting in a reduction in oxygen saturation in arterial blood.”
Prof Cristina Parolin, from the Department of Molecular Medicine of the University of Padua comments, “It should be added that the infection of hepatic pericytes by SARS-CoV-2, although not productive, i.e. not releasing infectious viral particles, stimulated a series of secretory functions on the part of the pericytes which were found to be relevant for the hemodynamic alterations of the circulation hepatopulmonary.”
One of the first and most important outbreaks in Europe had developed in the province of Bergamo, more than 70,000 people had died from Covid-19 in just 4 months, from February to May 2020. Although the main cause of mortality was attributed to insufficient hypoxic respiratory syndrome due to acute respiratory distress syndrome (ARDS), small vessel thrombosis (microthrombosis) associated with severe functional impairment in multiple organs other than the lung, such as the heart and kidney, were reported. Microthrombosis was also observed in the liver, and although hepatic involvement was often present in Covid-19 patients, the significance of these alterations remained uncertain.
Prof Aurelio Sonzogni, Head of the Pathology Department of the ASST Bergamo offers a conclusion, ”for Bergamo, Covid-19 was an unprecedented tragedy as the virus took us by surprise and no one knew how to treat it or what level of damage it would cause. Despite hospital staff shortages, we decided to perform autopsies on patients who died from Covid-19. We were able to gather information on the type of damage induced on different organs, which led to a fundamental step in revealing how thrombosis of small vessels became evident as one of the most significant lesions in lethal forms of Covid.”
