ArticleRespiratory research2024
What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study.
Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Serial blood serum measurements of calprotectin and deoxyribonuclease in COVID-19 patients during hospitalization and recovery until one year: a prospective, multicenter, observational study.BMC infectious diseases · 2026Observational
- NET Biomarkers in COVID-19 and Post-COVID Syndrome: a Comprehensive Analysis.Journal of clinical immunology · 2026Article
- Neutrophil Dynamics in Viral Infections: Drivers of Inflammation and Targets for Pro-Resolving Therapies.Journal of innate immunity · 2026Review
- Neutrophil extracellular traps associated with severity and prognosis of community-acquired pneumonia.Clinical and experimental medicine · 2025Article
- Relationship of Circulatory Markers of NETosis with COVID-19 Severity: A Prospective Cohort Study.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2025Article
- Dysregulated Resolution of Inflammation After Respiratory Viral Infections: Molecular Pathways Linking Neuroinflammation to Post-Viral Neuropathic Pain-A Narrative Review.International journal of molecular sciences · 2025Review
- Context-dependent contribution of peptidyl arginine deiminase 4 (PAD4) to neutrophil extracellular trap formation and liver injury in acute and chronic hepatotoxicant challenge.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Neutrophil Extracellular Trap Markers in Post Mortem Lung Biopsies from COVID-19 Patients.International journal of molecular sciences · 2025Article
- NETosis: A key player in autoimmunity, COVID-19, and long COVID.Journal of translational autoimmunity · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Novel Methods for the Analysis of Serum NET Remnants: Evaluation in Patients with Severe COVID-19.International journal of molecular sciences · 2025Article
- Diabetic cardiomyopathy and COVID-19: intersecting pathways and amplified cardiovascular risk.Frontiers in pharmacology · 2025Review
- Neutrophil extracellular traps and macrophage activation contibute to thrombosis and post-covid syndrome in SARS-CoV-2 infection.Frontiers in immunology · 2025Article
- Post-COVID pulmonary injury in K18-hACE2 mice shows persistent neutrophils and neutrophil extracellular trap formation.Immunity, inflammation and disease · 2024Article
- The development of anticyclic citrullinated peptide (anti-CCP) antibody following severe COVID-19.Immunity, inflammation and disease · 2024Article
- What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study.Respiratory research · 2024Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, and there are scarce data on their evolution during the disease. We studied circulating NET markers in patients with COVID-19 throughout their hospitalization.
methodsWe prospectively included 93 patients (201 blood samples), evaluating the disease severity in 3 evolutionary phases (viral, early, and late inflammation). Of these, 72 had 180 samples in various phases. We also evaluated 55 controls with similar age, sex and comorbidities. We measured 4 NET markers in serum: cfDNA, CitH3, and MPO-DNA and NE-DNA complexes; as well as neutrophil-related cytokines IL-8 and G-CSF.
resultsThe COVID-19 group had higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), and cfDNA, MPO-DNA, and NE-DNA (7.87 vs 2.56 ng/mL; 0.80 vs 0.52 and 1.04 vs 0.72, respectively, p < 0.001 for all) than the controls throughout hospitalisation. cfDNA was the only NET marker clearly related to severity, and it remained higher in non-survivors during the 3 phases. Only cfDNA was an independent risk factor for mortality and need for intensive care. Neutrophil count, IL-8, and G-CSF were significantly related to severity. MPO-DNA and NE-DNA showed significant correlations (r: 0.483, p < 0.001), including all 3 phases and across all severity grades, and they only remained significantly higher on days 10-16 of evolution in those who died. Correlations among the other NET markers were lower than expected.
conclusionsThe circulating biomarkers of NETs were present in patients with COVID-19 throughout hospitalization. cfDNA was associated with severity and mortality, but the three other markers showed little or no association with these outcomes. Neutrophil activity and neutrophil count were also associated with severity. MPO-DNA and NE-DNA better reflected NET formation. cfDNA appeared to be more associated with overall tissue damage; previous widespread use of this marker could have overestimated the relationship between NETs and severity. Currently, there are limitations to accurate NET markers measurement that make it difficult to assess its true role in COVID-19 pathogenesis.
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