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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1507167

NEUTROPHIL EXTRACELLULAR TRAPS AND MACROPHAGE ACTIVATION CONTIBUTE TO THROMBOSIS AND POST-COVID SYNDROME IN SARS-CoV-2 INFECTION

Provisionally accepted
Irene Serrano-Gonzalo Irene Serrano-Gonzalo 1Barbara Menéndez-Jandula Barbara Menéndez-Jandula 2Esther Franco-Garcia Esther Franco-Garcia 3Isidro Arévalo-Vargas Isidro Arévalo-Vargas 1Carlos Lahoz-Gil Carlos Lahoz-Gil 4Paz Latre Paz Latre 4Sonia Roca-Esteve Sonia Roca-Esteve 4Ralf Köhler Ralf Köhler 5Laura Lopez de Frutos Laura Lopez de Frutos 4Pilar Giraldo Pilar Giraldo 5*
  • 1 Doctoral School, University of Zaragoza, Zaragoza, Aragon, Spain
  • 2 Hospital Universitario Miguel Servet, Zaragoza, Aragon, Spain
  • 3 Lozano Blesa University Clinical Hospital, Zaragoza, Aragon, Spain
  • 4 Fundación Española para Estudio y Terapéutica Enfermedad de gaucher y otras Lisosomales (FEETEG), Zaragoza, Aragon, Spain
  • 5 Aragonese Institute of Health Research, University of Zaragoza, Zaragoza, Spain

The final, formatted version of the article will be published soon.

    Background: SARS-CoV-2 infection activates macrophages and induces the release of neutrophil extracellular traps (NETs). Excess NETs is linked to inflammatory and thrombotic complications observed in COVID-19. Aim: to explore the impact of NETs and macrophage activation on SARS-CoV-2-infected patients who developed complications. Methods: We included 30 patients from the first (March 2020) and 30 from the second wave (July 2021), collecting two plasma samples at diagnosis and seven days later. Data on demographics, comorbidities, and basic analytical data were compiled. NETs markers (myeloperoxidase (MPO), neutrophil elastase (NE), p-selectin (P-SEL) and S100A8/S100A9 heterodimer (MRP)) and macrophage activation markers (Chitotriosidase activity (ChT), CCL18/PARC and YKL-40) were measured. Results: The first wave had higher incidences of post-COVID syndrome, ICU admissions, and mortality. Patients of each wave showed elevated blood cells, liver enzymes, and coagulation markers at the time of diagnosis, with fibrinogen and D-Dimer differing between waves. NET and macrophage markers, NE, MPO, MRP, DNAse, ChT, and CCL18 were elevated, while P-SEL, cfDNA, and YKL-40 were decreased if compared to controls. A decrease in NE and DNAse is a link to lower levels of these two markers in complications versus without complications. Conclusions: This study demostrates alterations in NETs and macrophage activation markers in COVID-19 patients, indicating an imbalance in inflammatory response regulation.

    Keywords: SARS-CoV-2,, neutrophils extracellular traps (NETs), Thrombosis, post-COVID syndrome, macrophage biomarkers

    Received: 07 Oct 2024; Accepted: 04 Feb 2025.

    Copyright: © 2025 Serrano-Gonzalo, Menéndez-Jandula, Franco-Garcia, Arévalo-Vargas, Lahoz-Gil, Latre, Roca-Esteve, Köhler, Lopez de Frutos and Giraldo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Pilar Giraldo, Aragonese Institute of Health Research, University of Zaragoza, Zaragoza, Spain

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