Richard Plem, Nicole de Buhr, Rabea Imker, Silke Akhdar, Marita Meurer, Christine S. Falk, Johanna Ernst, Maria M. Gabriel, Jana Keil, Verena Kopfnagel, Thomas Illig, Karin Weissenborn, Sabine Blaschke, Isabel Bröhl, Christoph Römmele, Gerrit M. Grosse, Ramona Schuppner
- Background: During the COVID-19 pandemic, it became evident that an infection with SARS-CoV-2 is associated with an increased predisposition for thrombembolic events. Recent studies suggest an excessive neutrophil extracellular trap (NET)-formation in response to SARS-CoV-2, which is considered a hallmark in immunothrombosis. A better understanding of the (dys)regulation of NET-formation in COVID-19 may provide the basis for new therapeutic strategies.
Methods: We conducted a pilot study with a total of 84 patients in three groups matched in a 1:1:1 fashion: Group 1: patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and SARS-CoV-2 infection, Group 2: patients with AIS and no SARS-CoV-2 infection and Group 3: patients with SARS-CoV-2 infection and no AIS or TIA. Venous blood samples were collected from all patients and subsequently analyzed for NET-specific markers, NET regulators (Deoxyribonuclease (DNase) activity) and a panel of cytokines.
Results:Background: During the COVID-19 pandemic, it became evident that an infection with SARS-CoV-2 is associated with an increased predisposition for thrombembolic events. Recent studies suggest an excessive neutrophil extracellular trap (NET)-formation in response to SARS-CoV-2, which is considered a hallmark in immunothrombosis. A better understanding of the (dys)regulation of NET-formation in COVID-19 may provide the basis for new therapeutic strategies.
Methods: We conducted a pilot study with a total of 84 patients in three groups matched in a 1:1:1 fashion: Group 1: patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and SARS-CoV-2 infection, Group 2: patients with AIS and no SARS-CoV-2 infection and Group 3: patients with SARS-CoV-2 infection and no AIS or TIA. Venous blood samples were collected from all patients and subsequently analyzed for NET-specific markers, NET regulators (Deoxyribonuclease (DNase) activity) and a panel of cytokines.
Results: Citrullinated histone3 (H3cit) and elastase levels were higher in groups with SARS-CoV-2 infection (Groups 1 and 3) compared to patients without ((group 1: H3cit = 2.9 (1.11-6.89) ng/mL, elastase = 312.1 (162-435.4) ng/mL and group 3: H3cit = 3.31 (2.03-7.97) ng/mL and elastase = 433.1 (281-783.8) ng/mL) vs. group 2: H3cit = 1.17 (0.61-2.15) ng/mL), elastase = 195.1 (91.99-386.9) ng/mL). No relevant differences were found regarding other measured NET-marker (myeloperoxidase, LL-37). DNase activity was lower in group 1 (6.12 (4.97-6.78) pmol/mL/min) compared to both other groups (group 2: (7.16 (5.88-7.85) pmol/mL/min) (p=0.018) and group 3 (7.19 (5.52-8.54) pmol/mL/min) (p=0.013).
Conclusion: This pilot data suggest that a disturbed regulation of NETs in patients with SARS-CoV-2 infection may play a role in SARS-CoV-2 associated cerebral ischemia. These results highlight the importance of further investigating the role of NETs in immunothrombosis in the context of viral infections, to better understand its potential as a target for therapeutic strategies.…
