Extracellular Vesicles and Citrullinated Histone H3 in Coronavirus Disease 2019 (COVID-19) Patients

Background : Pulmonary thrombus formation is a hallmark of COVID-19. A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear. Aims : To evaluate the role of extracellular vesicles (EV) and citrullinated histone H3 (citH3) as markers of coagulopathy and inflammation. Methods : We studied 41 adult COVID-19 patients with a positive result on a reverse-transcriptase polymerase-chain-reaction assay and 37 sex-and age-matched healthy controls. Number and surface characteristics of EV and citH3 levels were determined in plasma upon admission by flowcytometry and immunoassay, respectively. Values are given as median (25 th , 75 th percentile) and differences by geometric mean ratios (GMR [95% CI]) or mean differences (ΔsMean [95% CI]). Results : 20 patients had severe and 21 mild disease. Patients exhibited significantly higher numbers of total EV, and of EV derived from platelets, endothelial cells, leukocytes, or neutrophils than controls (Table 1). EV from alveolar-macrophages and alveolar-epithelial-cells were detectable in plasma and were significantly higher in patients. ICAM-1 positive EV levels were higher in patients while no difference between TF-positive and ACE-positive EV was seen between the two groups. Levels of EV did not differ between patients with severe and mild COVID-19. citH3 levels were higher in patients than in controls [1.42 (0.6, 3.37) vs 0.31 (0.14, 0.6), GMR 4.44 (2.57, 7.66);P < 0.001], and were significantly lower in patients with mild disease compared to those with severe disease. Conclusions : EV and citH3 are associated with COVID-19. They provide information regarding pathophysiology and could be explored as markers of the disease.