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Increased serum citrullinated histone H3 levels in COVID-19 patients with acute ischemic stroke
Muhammet Duran Bayar1, Aysel Büşra Şişman1, Gizem Koral2
1Department of Neurology, Haseki Research and Training Hospital, Health Sciences University, Istanbul, Turkey.
Insights
Neutrophil extracellular trap (NET) formation is elevated in COVID-19 patients experiencing acute ischemic stroke (AIS). While NETosis may increase thrombosis risk, its markers lack prognostic value in these patients.
Area of Science:
- Neurology
- Immunology
- Infectious Diseases
Background:
- Coronavirus disease 2019 (COVID-19) is associated with an increased prevalence of acute ischemic stroke (AIS).
- A leading hypothesis suggests that virus-induced hypercoagulation contributes to arterial thrombosis in COVID-19 patients.
- Neutrophil extracellular trap (NET) formation, or NETosis, is implicated in inflammatory and thrombotic processes.
Purpose of the Study:
- To investigate the role of NETosis in the pathogenesis of AIS in patients with COVID-19.
- To assess serum levels of NETosis markers and associated mediators in different patient cohorts.
Main Methods:
- Serum levels of citrullinated histone H3 (H3Cit), IL-8, and C5a were measured using ELISA.
- Patients included: 26 COVID-19+ pneumonia with AIS, 32 COVID-19+ pneumonia without AIS, and 24 AIS without COVID-19.
- Clinical characteristics and inflammatory markers were collected and analyzed.
Main Results:
- Significantly higher H3Cit levels were observed in COVID-19+ AIS patients compared to controls.
- IL-8 and C5a levels were comparable across all study groups.
- COVID-19+ AIS patients exhibited elevated white blood cell, lymphocyte, neutrophil, D-dimer, C-reactive protein, and procalcitonin levels.
Conclusions:
- Elevated H3Cit levels in COVID-19 related AIS suggest NETosis may contribute to arterial thrombosis susceptibility.
- H3Cit levels did not correlate with clinical severity or inflammation parameters, limiting their prognostic value.
- The association between IL-8 and NETosis appears disrupted in AIS patients.
Background And Purpose:
Prevalence of acute ische-mic stroke (AIS) is increased in patients with coronavirus disease 2019 (COVID-19). A proposed hypothesis is increased virus-induced propensity to hypercoagulation resulting in arterial thrombosis. Our aim was to provide evidence regarding the involvement of neutrophil extracellular trap (NET) formation (NETosis) in COVID-19 related AIS.
Methods:
Twenty-six consecutively enrolled COVID-19+ pneumonia patients with AIS, 32 COVID-19+ pneumonia patients without AIS and 24 AIS patients without COVID-19 infection were included to the study. Clinical characteristics of recruited patients were collected. Serum levels of citrullinated histone H3 (H3Cit; a factor of NETosis), IL-8 and C5a (mediators associated with NETosis) were measured by ELISA (enzyme-linked immunosorbent assay).
Results:
H3Cit levels were significantly higher in COVID-19+ AIS patients, whereas all study groups showed comparable IL-8 and C5a levels. There were no significant differences among etiological subgroups of AIS patients with or without COVID-19. AIS patients with COVID-19 showed relatively increased white blood cell, lymphocyte, neutrophil, D-dimer, C-reactive protein and procalcitonin levels than control groups. H3Cit levels did not correlate with clinical/prognostic features and inflammation parameters. H3Cit and IL-8 levels were correlated in COVID-19 patients without stroke but not in COVID-19 positive or negative AIS patients.
Conclusion:
Increased levels of inflammation parameters and H3Cit in COVID-19 related AIS suggest that NETosis may cause susceptibility to arterial thrombosis. However, H3Cit levels do not correlate with clinical severity measures and inflammation parameters diminishing the prognostic biomarker value of NETosis factors. Moreover, the link between IL-8 and NETosis appears to be abolished in AIS.
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