ArticleJCI insight2022
Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.
Open access · goldAbstract readMulticenter Study
In one paragraph
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Delving into the clinical impact of NETs in pediatric cancer.Pediatric research · 2025Pooled it
- Epigenetic Regulation of the NET Formation-Blood-Brain Barrier Axis in Ischemic Stroke: Mechanisms, Therapeutic Targets and Translational Perspectives.Neurology international · 2026Review
- Prospective multicentre study of upper respiratory mucosal transcriptomics reveals two major endotypes of critically ill COVID-19 patients.Communications medicine · 2026Article
- Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.Biomedicines · 2025Review
- Neutrophil Extracellular Traps in Pediatric Infections: A Systematic Review.Current issues in molecular biology · 2025Review
- Soluble CD13 is a potential mediator of neutrophil-induced thrombogenic inflammation in SARS-CoV-2 infection.JCI insight · 2025Article
- A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs.Cells · 2025Article
- Neutrophils restricted contribution ofHeliyon · 2025Article
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- Clinical characteristics and risk factors of severe COVID-19 in hospitalized neonates with omicron variant infection: a retrospective study.Italian journal of pediatrics · 2024Article
- Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease.Journal of translational medicine · 2024Article
- What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study.Respiratory research · 2024Article
- Endothelial Damage, Neutrophil Extracellular Traps and Platelet Activation in COVID-19 vs. Community-Acquired Pneumonia: A Case-Control Study.International journal of molecular sciences · 2023Article
- Review
- Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC).eLife · 2023Review
- Statin Therapy in COVID-19: Inhibition of NETosis.Journal of general internal medicine · 2023Article
- What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant?Diagnostic pathology · 2023Article
- DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat.PloS one · 2023Article
- Course and outcome of chilblain-like acral lesions during COVID-19 pandemic.Journal of the European Academy of Dermatology and Venereology : JEADV · 2023Article
- Metformin therapy in COVID-19: inhibition of NETosis.Journal of thrombosis and thrombolysis · 2022Article
Corrections and comments
- Update of
Authors and funding
55 authors at 19 institutions in 4 countries.
Carmelo Carmona-RiveraSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
Yu ZhangHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID); and.
Kerry DobbsLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Tovah E MarkowitzAxle Informatics, Bethesda, Maryland, USA.
Clifton L DalgardDepartment of Anatomy, Physiology & Genetics, School of Medicine, and the American Genome Center, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USA.
Andrew J OlerBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Maryland, USA.
Dillon R ClaybaughSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
Deborah DraperLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Meng TruongLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Ottavia M DelmonteLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Francesco LicciardiDepartment of Public Health and Pediatric Sciences and.
Ugo RamenghiDepartment of Public Health and Pediatric Sciences and.
Nicoletta CrescenzioPediatric Hematology, "Regina Margherita" Children Hospital, University of Turin, Turin, Italy.
Luisa ImbertiCentro di Ricerca Emato-oncologica AIL, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Alessandra SottiniCentro di Ricerca Emato-oncologica AIL, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Virginia QuaresimaCentro di Ricerca Emato-oncologica AIL, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Chiara FioriniCentro di Ricerca Emato-oncologica AIL, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
Valentina DiscepoloDepartment of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy.
Andrea Lo VecchioDepartment of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy.
Alfredo GuarinoDepartment of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy.
Luca PierriDepartment of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy.
Andrea CatzolaDepartment of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy.
Andrea BiondiDepartment of Pediatrics, University of Milano-Bicocca, European Reference Network (ERN) PaedCan, EuroBloodNet, MetabERN, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
Paolo BonfantiDepartment of Infectious Diseases, San Gerardo Hospital-University of Milano-Bicocca, Monza, Italy.
Maria C Poli HarlowePrograma de Inmunogenética e Inmunología Traslacional, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.
Yasmin EspinosaHospital Roberto del Rio, Santiago, Chile.
Camila AstudilloHospital Roberto del Rio, Santiago, Chile.
Emma Rey-JuradoPrograma de Inmunogenética e Inmunología Traslacional, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.
Cecilia VialFacultad de Medicina Clínica Alemana Universidad del Desarrollo, Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina, Santiago, Chile.
Javiera de la CruzPrograma de Inmunogenética e Inmunología Traslacional, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.
Ricardo GonzalezPediatric Intensive Care Unit, Hospital Exequiel Gonzalez Cortés, Santiago, Chile.
Cecilia PineraInfectious Diseases Unit, Hospital Dr. Exequiel González Cortés, Región Metropolitana, Chile.
Jacqueline W MaysNational Institute of Dental and Craniofacial Research (NIDCR), NIH, Bethesda, Maryland, USA.
Ashley NgDepartment of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Andrew PlattEmerging Pathogens Section, Critical Care Medicine Department, Clinical Center, and Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA.
NIH COVID Autopsy Consortium
COVID STORM Clinicians
Beth DroletDepartment of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
John MoonDepartment of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Edward W CowenDermatology Branch, NIAMS.
Heather KenneyLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Sarah E WeberLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Riccardo CastagnoliLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Mary MaglioccoMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID; and.
Michael A StackMolecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID; and.
Gina MontealegreDivision of Clinical Research, NIAID, NIH, Bethesda, Maryland, USA.
Karyl BarronDivision of Clinical Research, NIAID, NIH, Bethesda, Maryland, USA.
Danielle L FinkApplied/Developmental Research Directorate, Frederick and National Laboratory for Cancer Research, National Cancer Institute (NCI), NIH, Frederick, Maryland, USA.
Douglas B KuhnsApplied/Developmental Research Directorate, Frederick and National Laboratory for Cancer Research, National Cancer Institute (NCI), NIH, Frederick, Maryland, USA.
Stephen M HewittLaboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA.
Lisa M ArkinDepartment of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Daniel S ChertowEmerging Pathogens Section, Critical Care Medicine Department, Clinical Center, and Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA.
Helen C SuHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID); and.
Luigi D NotarangeloLCIM, NIAID, NIH, Bethesda, Maryland, USA.
Mariana J KaplanSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
National Institutes of Health · USUniversity of Naples Federico II · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITUniversidad del Desarrollo · CLUniversity of Wisconsin–Madison · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USFrederick National Laboratory for Cancer Research · USHospital Roberto del Rio · CLImmune Regulation (United Kingdom) · GBNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health Clinical Center · USUniversity of Milano-Bicocca · ITAmerican Axle & Manufacturing (United States) · USCenter for Cancer Research · USNational Institute of Dental and Craniofacial Research · USNaval Research Laboratory Information Technology DivisionOspedale Regina Margherita · ITUniformed Services University of the Health Sciences · USUniversity of Chile · CL
Funding
Systemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5MImmunobiology and therapy of oral mucosal and salivary gland chronic graft-versus-host diseaseZIADE000747 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI MAYS, JACQUELINE · 2016 to 2025
$14.9MHost factors contributing to susceptibility to COVID-19 diseaseZIAAI001265 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2020 to 2025
$9.5MDermatology Consultation ServiceZIAAR041229 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI COWEN, EDWARD · 2022 to 2025
$4.0MCharacterization of host immune responses to SARS-CoV-2ZIAAI001270 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2020 to 2025
$1.2MIntramural NIH HHS ZIA AI001265Intramural NIH HHS ZIA AI001270Intramural NIH HHS ZIA AR041199Intramural NIH HHS ZIA DE000747
Abstract
Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.
Indexed as
COVID-19Extracellular TrapsActinsAdultChildDeoxyribonuclease IHumansNeutrophilsSARS-CoV-2Systemic Inflammatory Response SyndromeActinsDeoxyribonuclease IInfectious diseaseInflammationNeutrophils
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