The role of complement and extracellular vesicles in the development of pulmonary embolism in severe COVID-19 cases

Complement and extracellular vesicles (EVs) association with thrombogenic tendencies is acknowledged, but limited evidence exists for their link to COVID-19 venous thromboembolism. This study aims to examine the relationship between pulmonary embolism and the expression of complement and other proteins related to thrombogenesis in severe Covid-19 patients. We included prospectively 207 severe COVID-19 patients and retrospectively screened for pulmonary embolism (PE). This analysis comprises 20 confirmed PE cases and 20 matched patients without PE. Blood samples taken at the admission in the intensive care unit were analyzed for complement using ELISA. EVs derived from neutrophils, endothelium, or platelets, as well carrying complement or tissue factor were analyzed using flow cytometry. Complement levels were markedly elevated, with a notable increase in C3a and Terminal Complement Complex. The most prevalent EV population was identified as tissue factor (TF)-carrying EVs which peaked in patients with PE during ICU days 4-9. However, for both the complement and analyzed EV populations, no statistically significant differences were found between the patients who developed pulmonary embolism and those who did not. In conclusion, complement factors and EVs expressing tissue factor, along with EVs derived from endothelial cells and platelets, are elevated in severe COVID-19 patients, regardless of the presence of pulmonary embolism. However, the involvement of complement and procoagulant EVs in peripheral plasma in the development of pulmonary embolism is still unclear and requires further investigation.