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The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies
Emily Parissa Ghanbari1,2, Kai Jakobs1,2, Marianna Puccini1,2
1Department of Cardiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203 Berlin, Germany.
Insights
Neutrophil extracellular traps (NETosis) and complement markers are elevated in COVID-19 patients, distinguishing them from other infections. These markers correlate with disease severity and may identify patients at risk for immunothrombosis.
Area of Science:
- Immunology
- Pathology
- Infectious Diseases
Background:
- Inflammation-induced coagulopathy is a significant complication of COVID-19.
- Neutrophil extracellular traps (NETosis) and complement activation are implicated in COVID-19 pathogenesis.
- Understanding the interplay between NETosis, complement, and thrombogenicity is crucial for managing severe COVID-19.
Purpose of the Study:
- To evaluate the association between NETosis and complement markers in COVID-19 patients.
- To investigate the relationship of these markers with thrombogenicity and disease severity.
- To differentiate COVID-19 from other pulmonary infections based on NETosis and complement profiles.
Main Methods:
- Comparative study of hospitalized patients with SARS-CoV-2 infection (COVpos) and other respiratory infections (COVneg).
- Measurement of NETosis markers (MPO/DNA complexes), coagulation parameters, platelet counts, and complement markers (C3, C5, C5b-9).
- Correlation analysis between markers and clinical severity scores (SOFA).
Main Results:
- NETosis, coagulation, platelet, and complement markers were significantly elevated in COVpos patients, particularly those with severe disease.
- NETosis markers correlated with coagulation, platelet, and complement markers specifically in COVpos patients.
- Complement markers (C3, C5, C5b-9) showed significant associations with disease severity (SOFA score) in severely ill COVpos patients.
Conclusions:
- NETosis and the complement system are integral to COVID-19 inflammation and clinical severity.
- Elevated NETosis and complement markers distinguish COVID-19 from other pulmonary infections.
- Complement marker C5 may serve as a potential biomarker for identifying COVID-19 patients at high risk for immunothrombosis.
Abstract:
Inflammation-induced coagulopathy is a common complication associated with coronavirus disease 2019 (COVID-19). We aim to evaluate the association of NETosis and complement markers with each other as well as their association with thrombogenicity and disease severity in COVID-19. The study included hospitalized patients with an acute respiratory infection: patients with SARS-CoV2 infection (COVpos, n = 47) or either pneumonia or infection-triggered acute exacerbated COPD (COVneg, n = 36). Our results show that NETosis, coagulation, and platelets, as well as complement markers, were significantly increased in COVpos patients, especially in severely ill COVpos patients. NETosis marker MPO/DNA complexes correlated with coagulation, platelet, and complement markers only in COVpos. Severely ill COVpos patients showed an association between complement C3 and SOFA (R = 0.48; p ≤ 0.028), C5 and SOFA (R = 0.46; p ≤ 0.038), and C5b-9 and SOFA (R = 0.44; p ≤ 0.046). This study provides further evidence that NETosis and the complement system are key players in COVID-19 inflammation and clinical severity. Unlike previous studies that found NETosis and complement markers to be elevated in COVID-19 patients compared to healthy controls, our findings show that this characteristic distinguishes COVID-19 from other pulmonary infectious diseases. Based on our results, we propose that COVID-19 patients at high risk for immunothrombosis could be identified via elevated complement markers such as C5.
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