The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies

• Published in: Biomedicines Vol. 11; no. 5; p. 1371
• Main Authors: Ghanbari, Emily Parissa, Jakobs, Kai, Puccini, Marianna, Reinshagen, Leander, Friebel, Julian, Haghikia, Arash, Kränkel, Nicolle, Landmesser, Ulf, Rauch-Kröhnert, Ursula
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05-05-2023; MDPI
• Subjects: Blood clots; Blood platelets; Chronic obstructive pulmonary disease; Coagulation; complement; Complement activation; Complement component C3; Complement component C5; Coronaviruses; COVID-19; Diseases; Health aspects; Hospital patients; Infections; Infectious diseases; Inflammation; Lung diseases; Lung diseases, Obstructive; Medical research; Medicine, Experimental; NETosis; Neutrophils; Pathogens; Patients; Platelets; Pneumonia; Proteins; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Thromboembolism; Thrombosis; Viral infections; United States > US; Switzerland; COVID-19; NETosis; complement; coagulation
• DOI: 10.3390/biomedicines11051371
• EISSN: 2227-9059

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,
= 47) or either pneumonia or infection-triggered acute exacerbated COPD (COVneg,
= 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;
≤ 0.028), C5 and SOFA (R = 0.46;
≤ 0.038), and C5b-9 and SOFA (R = 0.44;
≤ 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.