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Published on: September 22, 2023
Extracellular Vesicles and Citrullinated Histone H3 in Coronavirus Disease 2019 Patients
Ludwig Traby1, Marietta Kollars1, Manuel Kussmann1
1Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Insights
Extracellular vesicles (EVs) and citrullinated histone H3 are elevated in COVID-19 patients, indicating their role in disease pathophysiology. These markers, particularly citrullinated histone H3, may help differentiate disease severity.
Area of Science:
- Cardiovascular Science
- Immunology
- Virology
Background:
- Pulmonary thrombus formation is a key feature of COVID-19, linked to immune dysregulation and thromboinflammation.
- The precise pathomechanisms underlying COVID-19-associated thromboinflammation remain incompletely understood.
Purpose of the Study:
- To investigate the role of extracellular vesicles (EVs) and citrullinated histone H3 in COVID-19 pathophysiology.
- To determine if these markers correlate with disease severity.
Main Methods:
- Studied 41 adult COVID-19 patients and 37 healthy controls.
- Quantified plasma extracellular vesicle (EV) numbers and surface markers using flow cytometry.
- Measured citrullinated histone H3 levels via immunoassay.
Main Results:
- COVID-19 patients exhibited significantly higher numbers of EVs, including those derived from platelets, endothelial cells, and leukocytes, compared to controls.
- Elevated levels of citrullinated histone H3 were observed in COVID-19 patients.
- Citrullinated histone H3 levels were significantly lower in nonsevere COVID-19 cases compared to severe cases.
Conclusions:
- Extracellular vesicles (EVs) and citrullinated histone H3 are associated with COVID-19.
- These markers may offer insights into the disease's pathophysiology and severity.
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 (EVs) and citrullinated histone H3 levels were determined in plasma upon inclusion by flow cytometry and immunoassay.
Results:
In total, 20 patients had severe and 21 nonsevere 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 EVs derived from platelets, endothelial cells, leukocytes, or neutrophils than controls. EVs 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 nonsevere COVID-19. Citrullinated histone H3 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 nonsevere disease compared with those with severe disease.
Conclusion:
EV and citrullinated histone H3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease.
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