Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis

Area of Science:

• Immunology
• Hematology
• Pathophysiology

Background:

• Emerging evidence links complement and neutrophils to severe COVID-19 outcomes.
• Hyperinflammation and thrombotic microangiopathy are key contributors to COVID-19 mortality.

Purpose of the Study:

• To investigate the interaction between complement and the platelet/neutrophil extracellular traps (NETs)/thrombin axis in COVID-19.
• To elucidate the role of NETs and complement in COVID-19-associated immunothrombosis.

Main Methods:

• Analysis of COVID-19 patient specimens.
• Cell-based inhibition studies.
• Co-culture of NETs with human aortic endothelial cells (HAECs).

Main Results:

• Elevated plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 in COVID-19 patients.
• COVID-19 patient neutrophils expressed high TF and released TF-bearing NETs.
• COVID-19 plasma induced TF-bearing NETs, promoting HAEC thrombotic activity.
• Complement C3 inhibition disrupted TF expression in neutrophils.

Conclusions:

• Complement and NETs play a pivotal role in COVID-19 immunothrombosis.
• Targeting complement or NETosis presents a potential therapeutic strategy for severe COVID-19.