P1651: IMPACT OF NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AND MACROPHAGE ACTIVATION IN THE THROMBOTIC EVENTS IN COVID-19 PATIENTS

Abstract

Abstract Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: As part of the immune response induced by SARS-CoV-2 infection, neutrophils release extracellular traps (NETs) to fight infection and prevent its spread. An excess of NETs is associated with inflammatory and thrombotic complications, phenomena observed in COVID-19. Aims: To evaluate the expression of NET-associated molecules and other markers of macrophage activity, and to correlate them with clinical and classical laboratory determinations, in patients infected in two different waves. Methods: Two samples (at diagnosis and 7 days later) of plasma were obtained from 60 patients, half of whom were infected in March’20 and the rest in July’21. Demographic data, comorbidities, and basic analytical data were collected from the clinical history. At present we have performed a clinical follow-up of these patients analyzing the presence of thrombotic events, reactions to vaccination, post-COVID syndrome, and other complications. NETs were assessed by myeloperoxidase (MPO), neutrophil elastase (NE), p-selectin (P-SEL), and S100A8/S100A9 heterodimer (MPR). Chitotriosidase activity (ChT), CCL18/PARC, and YKL-40 were used to assess macrophage activation. All determinations were performed by immunoquantification or fluorometric assays. Non-parametric tests were used to evaluate the differences between waves, in the follow-up of the patients and to analyze the existence of correlations with the data from the laboratory. Values of p<0.05 were considered statistically significant. Results: Differences were observed between patients in the two waves -at diagnosis- in relation to molecules associated with NETs and macrophage activation, as well as for platelet and fibrinogen D quantification. Follow-up of the patients revealed significant differences in leukocyte and platelet counts, TTP, liver enzymes, and CRP. Patients in March’20 also showed differences in NE, INR, and PT, while those in July’21 showed differences in P-Sel, fibrinogen D, procalcitonin, and LDH concentrations. A significant correlation was observed between molecules associated with macrophage activity and coagulation parameters in patients in March’20 (ChT-INR-TP) and, with respect to NETs and coagulation in those in July’21 (PSel-Platelets). A total of two patients with thrombotic events was observed, one in the first wave and other in the second (3.3% on each wave) and three present a post-COVID syndrome, one in the first and two in the second wave (3.3% and 6.7% respectively). Ten patients died (16.7%), nine in the first and one in the second wave (30% and 3.3% respectively), 8 of them from causes related to the infection. Summary/Conclusion: This study demonstrates an alteration in NETs and macrophage activation in patients with COVID-19, which evolves over time and correlates with coagulation markers. The correlation of these alterations with the complications detected is being analyzed. This work has been financed with a grant from FEETEG. Keywords: Macrophage, Neutrophil, Thrombosis, COVID-19