LAUSR

Objectives Pulmonary thrombus formation is a hallmark of coronavirus disease 2019 (COVID-19). A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear. Methods We studied 41 adult COVID-19 patients with positive results on reverse-transcriptase polymerase-chain-reaction assays and 37 sex-and age-matched healthy controls. Number and surface characteristics of extracellular vesicles (EV) and citrullinated histone H 3 levels were determined in plasma upon inclusion by flowcytometry and immunoassay. Results 20 patients had severe and 21 non-severe disease. The number of EV [median, (25th, 75th percentile)] was significantly higher in patients compared with controls [658.8 (353.2, 876.6) vs 435.5 (332.5, 585.3), geometric mean ratio (95% confidence intervals): 2.6 (1.9, 3.6); p<0.001]. Patients exhibited significantly higher numbers of EV derived from platelets, endothelial cells, leukocytes, or neutrophils than controls. EV from alveolar-macrophages and alveolar-epithelial-cells were detectable in plasma and were significantly higher in patients. Intercellular Adhesion Molecule 1-positive EV levels were higher in patients, while no difference between tissue factor-positive and angiotensin converting enzyme-positive EV was seen between both groups. Levels of EV did not differ between patients with severe and non-severe COVID-19. Citrullinated histone H 3 levels [ng/ml, median (25th, 75th percentile)] were higher in patients than in controls [1.42 (0.6, 3.4) vs 0.31 (0.1, 0.6), geometric mean ratio: 4.44 (2.6, 7.7); p<0.001], and were significantly lower in patients with non-severe disease compared to those with severe disease. Conclusion EV and citrullinated histone H 3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease.