ArticleEBioMedicine2021
Defective NET clearance contributes to sustained FXII activation in COVID-19-associated pulmonary thrombo-inflammation.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 3 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Neutrophil Extracellular Traps in Viral Infections.Pathogens (Basel, Switzerland) · 2025Pooled it
- Cell-free DNA as diagnostic and prognostic biomarkers for adult sepsis: a systematic review and meta-analysis.Scientific reports · 2023Pooled it
- COVID-19 Vasculitis and vasculopathy-Distinct immunopathology emerging from the close juxtaposition of Type II Pneumocytes and Pulmonary Endothelial Cells.Seminars in immunopathology · 2022Pooled it
- Trial
- Involvement of the contact pathway in COVID-19 coagulopathy.Internal and emergency medicine · 2026Article
- Hyperacute Interleukin-1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion.Annals of neurology · 2026Article
- Mast cells release DNA Extracellular Traps (DETs) in response to SARS-CoV-2 and its spike protein.Cell communication and signaling : CCS · 2026Article
- 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
- SARS-Cov-2 Replication in a Blood-Brain Barrier Model Established with Human Brain Microvascular Endothelial Cells Induces Permeability and Disables ACE2-Dependent Regulation of Bradykinin B1 Receptor.International journal of molecular sciences · 2025Article
- Nerve- and airway-associated interstitial macrophages mitigate SARS-CoV-2 pathogenesis via type I interferon signaling.Immunity · 2025Article
- Neutrophil Extracellular Traps Capturing SARS-CoV-2 in the Lung Tissue (Alveoli and Parenchyma) Cause Microthrombi - A Strategy to Eliminate SARS-CoV-2 From the Circulation as Degraded Fibrin Clots.Circulation reports · 2025Article
- Efficient and scalable construction of clinical variable networks for complex diseases with RAMEN.Cell reports methods · 2025Article
- Neutrophils: Linking Inflammation to Thrombosis and Unlocking New Treatment Horizons.International journal of molecular sciences · 2025Review
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- The Role of Thrombo-inflammation in Ischemic Stroke: Focus on the Manipulation and Clinical Application.Molecular neurobiology · 2025Review
- Sepsis-induced NET formation requires MYD88 but is independent of GSDMD and PAD4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Thromboembolic Events in the Era of COVID-19: A Detailed Narrative Review.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Review
- Thromboinflammation vs. immunothrombosis: strategies for overcoming anticoagulant resistance in COVID-19 and other hyperinflammatory diseases. Is ROTEM helpful or not?Frontiers in immunology · 2025Review
- The endothelial-immunothrombotic storm in viral sepsis: lessons from COVID-19.Frontiers in immunology · 2025Review
- The Interaction of Complement and Intrinsic Coagulation System: A Comparative Study between COVID-19 and Bacterial Sepsis Patients.Journal of clinical medicine · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundCoagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood.
methodsWe performed proteomic analysis and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We further compared coagulation factor XII (FXII) and DNase activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced FXII activation using a chromogenic substrate assay.
findingsFXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients. In agreement with this, plasmaaac acafajföeFXII activation (FXIIa) was increased in samples from COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially due to impaired NET clearance by extracellular DNases as DNase substitution improved NET dissolution and reduced FXII activation in vitro.
interpretationCollectively, our study supports that the NET/FXII axis contributes to the pathogenic chain of procoagulant and proinflammatory responses in COVID-19. Targeting both NETs and FXIIa may offer a potential novel therapeutic strategy.
fundingThis study was supported by the European Union (840189), the Werner Otto Medical Foundation Hamburg (8/95) and the German Research Foundation (FR4239/1-1, A11/SFB877, B08/SFB841 and P06/KFO306).
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