ArticleThe Journal of experimental medicine2020
SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology.
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In one paragraph
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 618 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
618citing papers in PubMed, 2 pooled it
60.5field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
618 citing papers in PubMed, 2 syntheses or guidelines pooled it, 963 citations in OpenAlex.
- Neutrophil Extracellular Traps in Viral Infections.Pathogens (Basel, Switzerland) · 2025Pooled it
- Systemic cytokines drive conserved severity-associated myeloid responses across bacterial and viral infections.Communications biology · 2025Pooled it
- Multicenter randomized trial assessing efficacy and safety of aerosolized dornase Alfa in COVID-19 ARDS.Scientific reports · 2025Trial
- Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease.Nature communications · 2024Trial
- A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2.Annals of internal medicine · 2024Trial
- Surface proteome of plasma extracellular vesicles differentiates between SARS-CoV-2 and influenza infection.Virulence · 2026Article
- Is COVID-19 Infection A Risk Factor for Intubation-Related Acquired Airway Stenosis?Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases.Brain sciences · 2026Review
- Persistent NET states link lesion-related microbial signals to the cold tumor-related local restrictive environment: a context-dependent working model.Cell communication and signaling : CCS · 2026Review
- NETosis associates with human TB lung tissue destruction and disease pathogenesis.EMBO molecular medicine · 2026Article
- Impact of Neutrophil Extracellular Traps on Clinical Outcome after Subarachnoid Hemorrhage: A Translational Narrative Review.Translational stroke research · 2026Review
- Differential effects of SARS-CoV-2-targeted infection of ATII, club cells, and macrophages on lung immunopathology and antiviral responses.Mucosal immunology · 2026Article
- Mast cells release DNA Extracellular Traps (DETs) in response to SARS-CoV-2 and its spike protein.Cell communication and signaling : CCS · 2026Article
- Neutrophil extracellular traps promote macrophage activation through Toll-like receptor engagement and PKA and NF-kB signaling pathways.Cell communication and signaling : CCS · 2026Article
- Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.iScience · 2026Review
- Cell-free nucleic acids as a non-invasive biomarker for predicting COVID-19 disease severity and outcome: a retrospective cohort study.BMC infectious diseases · 2026Article
- Review
- Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response.iScience · 2026Article
- Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Type 2 immune history imprints local training in nerve and airway associated interstitial macrophages (NAMs) for disease tolerance during lethal respiratory viral infection.Research square · 2026Article
558 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
46 authors at 2 institutions in 1 country.
Flavio Protasio VerasCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Marjorie Cornejo PontelliVirology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Camila Meirelles SilvaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Juliana E Toller-KawahisaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Mikhael de LimaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Daniele Carvalho NascimentoCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Ayda Henriques SchneiderCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Diego CaetitéCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Lucas Alves TavaresVirology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Isadora M PaivaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Roberta RosalesDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
David ColónCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Ronaldo MartinsVirology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Italo Araujo CastroVirology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Glaucia M AlmeidaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Maria Isabel Fernandes LopesDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Maíra Nilson BenattiDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Letícia Pastorelli BonjornoDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Marcela Cavichioli GianniniDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Rodrigo Luppino-AssadDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Sérgio Luna AlmeidaDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Fernando VilarDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Rodrigo SantanaDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Valdes R BollelaDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Maria Auxiliadora-MartinsDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Marcos BorgesDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Carlos Henrique MirandaDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Antônio Pazin-FilhoDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Luis Lamberti P da SilvaVirology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Larissa Dias CunhaDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Dario S ZamboniCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Felipe Dal-PizzolLaboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil.
Luiz O LeiriaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Li SiyuanPathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Sabrina BatahPathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Alexandre FabroPathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Thais MauadDepartment Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
Marisa DolhnikoffDepartment Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
Amaro Duarte-NetoDepartment Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
Paulo SaldivaDepartment Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
Thiago Mattar CunhaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
José Carlos Alves-FilhoCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Eurico ArrudaVirology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Paulo Louzada-JuniorCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Renê Donizeti OliveiraDivisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Fernando Queiroz CunhaCenter of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Universidade de São Paulo · BRUniversidade do Sul de Santa Catarina · BR
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.
Indexed as
A549 CellsAdultAngiotensin-Converting Enzyme 2BetacoronavirusCell DeathCoronavirus InfectionsCOVID-19Epithelial CellsExtracellular TrapsFemaleHeLa CellsHumansMaleNeutrophil ActivationPandemicsPeptidyl-Dipeptidase AACE2 protein, humanAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase ASerine Proteases
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