Evidence map›Paper›PMID 35714708›Full record

ArticleChest2022

Neutrophil Extracellular Traps, Local IL-8 Expression, and Cytotoxic T-Lymphocyte Response in the Lungs of Patients With Fatal COVID-19.

Ignacio Melero, María Villalba-Esparza, Borja Recalde-Zamacona, Daniel Jiménez-Sánchez, Álvaro Teijeira, Alan Argueta, Laura García-Tobar, Laura Álvarez-Gigli, Cristina Sainz, David Garcia-Ros and 18 more

Open access · hybridAbstract read
In one paragraph

Article in Chest, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 58 citations in OpenAlex.

  1. Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Exploring Neutrophil Extracellular Traps in Cardiovascular Pathologies: The Impact of Lipid Profiles, PAD4, and Radiation.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 8 institutions in 2 countries.

Ignacio MeleroDivision of Immunology and Immunotherapy, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Navarra Institute for Health Research, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
María Villalba-EsparzaNavarra Institute for Health Research, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Borja Recalde-ZamaconaService of Pulmonary Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
Daniel Jiménez-SánchezDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Álvaro TeijeiraDivision of Immunology and Immunotherapy, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Navarra Institute for Health Research, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
Alan ArguetaDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Laura García-TobarDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Laura Álvarez-GigliDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Cristina SainzDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
David Garcia-RosDepartment of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain.
Estefanía ToledoDepartment of Preventive Medicine and Public Health, IdiSNA, University of Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición, Institute of Health Carlos III, Madrid, Spain.
Marta Abengozar-MuelaDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Mirian Fernández-AlonsoNavarra Institute for Health Research, Pamplona, Spain; Department of Microbiology and Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain.
Mariano Rodríguez-MateosDepartment of Microbiology and Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain.
Gabriel ReinaNavarra Institute for Health Research, Pamplona, Spain; Department of Microbiology and Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain.
Francisco Carmona-TorreNavarra Institute for Health Research, Pamplona, Spain; Department of Microbiology and Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain.
Jorge Augusto QuirogaDepartment of Internal Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
Jose L Del PozoNavarra Institute for Health Research, Pamplona, Spain; Department of Microbiology and Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain.
Amy CrossNuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, England.
Álvaro López-JaneiroDepartment of Pathology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
David HardissonDepartment of Pathology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
José I EchevesteCentro de Investigación Biomédica en Red de Cáncer, Madrid, Spain; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain.
Maria D LozanoNavarra Institute for Health Research, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain.
Ling-Pei HoMRC Human Immunology Unit, University of Oxford, Oxford, England.
Paul KlenermanNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, Oxford, England.
Fadi IssaNuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, England.
Manuel F LandechoDepartment of Internal Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
Carlos E de AndreaNavarra Institute for Health Research, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain; Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain; Department of Anatomy, Physiology and Pathology, University of Navarra, Pamplona, Spain. Electronic address: ceandrea@unav.es.
Clinica Universidad de Navarra · ESCentro de Investigación Biomédica en Red de Cáncer · ESHospital Universitario La Paz · ESJohn Radcliffe Hospital · GBInstituto de Salud Carlos III · ESMedawar Building for Pathogen Research · GBUniversidad de Navarra · ESUniversity of Oxford · GB

Funding

Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ARTHUR Y KIM · 2009 to 2026
$48.1M
NIAID NIH HHS U19 AI082630Wellcome Trust
6 · The paper itself

Abstract

backgroundExcessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but have also been shown to mediate tissue damage in a number of diseases. RESEARCH QUESTION: Could NETs and their tissue-damaging properties inherent to neutrophil-associated functions play a role in the respiratory failure seen in patients with severe COVID-19, and how does this relate to the SARS-CoV-2 viral loads, IL-8 (CXCL8) chemokine expression, and cytotoxic T-lymphocyte infiltrates? STUDY DESIGN AND

methodsSixteen lung biopsy samples obtained immediately after death were analyzed methodically as exploratory and validation cohorts. NETs were analyzed quantitatively by multiplexed immunofluorescence and were correlated with local levels of IL-8 messenger RNA (mRNA) and the density of CD8+ T-cell infiltration. SARS-CoV-2 presence in tissue was quantified by reverse-transcriptase polymerase chain reaction and immunohistochemistry analysis.

resultsNETs were found in the lung interstitium and surrounding the bronchiolar epithelium with interindividual and spatial heterogeneity. NET density did not correlate with SARS-CoV-2 tissue viral load. NETs were associated with local IL-8 mRNA levels. NETs were also detected in pulmonary thrombi and in only one of eight liver tissues. NET focal presence correlated negatively with CD8+ T-cell infiltration in the lungs.

interpretationAbundant neutrophils undergoing NETosis are found in the lungs of patients with fatal COVID-19, but no correlation was found with viral loads. The strong association between NETs and IL-8 points to this chemokine as a potentially causative factor. The function of cytotoxic T-lymphocytes in the immune responses against SARS-CoV-2 may be interfered with by the presence of NETs.

Indexed as

COVID-19Extracellular TrapsHumansInterleukin-8LungNeutrophilsRNA, MessengerSARS-CoV-2T-Lymphocytes, CytotoxicInterleukin-8RNA, MessengerCOVID-19lungsneutrophil extracellular trapsneutrophilsSARS-CoV-2

Identifiers

PMID35714708
PMCPMC9197577
OpenAlexW4282933794

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.