ArticleJCI insight2021
Self-sustaining IL-8 loops drive a prothrombotic neutrophil phenotype in severe COVID-19.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials.Frontiers in immunology · 2022Pooled it
- Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID).Journal of general internal medicine · 2022Trial
- Proteomic analysis reveals divergent inflammatory mechanisms of COVID-associated Guillain-Barré syndrome.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Adenovirus phagocytosis by neutrophils triggers a pro-inflammatory response.PLoS pathogens · 2026Article
- Manuka honey and its component, methyl syringate, shift neutrophil release profiles from pro-inflammatory while preserving pro-regenerative growth factor releaseFrontiers in immunology · 2026Article
- Neutrophil Plasticity and NETosis in Tumour Microenvironment: Tumour Evolution and Therapy Resistance.Journal of immunology research · 2026Review
- Neutrophil extracellular traps associated with severity and prognosis of community-acquired pneumonia.Clinical and experimental medicine · 2025Article
- Biological Plausibility Between Long-COVID and Periodontal Disease Development or Progression.Biomedicines · 2025Review
- Bioinformatics analysis of the proteome in the pathway of complement and coagulation cascades in COVID-19: discovering potential biomarkers of FGB and SERPINA5.BMC infectious diseases · 2025Article
- Plasma Proteomic Profiling Yields a High-Performance Biomarker Panel for Predicting a Poor Prognosis in Patients with COVID-19.Journal of proteome research · 2025Article
- Clinical C3 Inhibition With AMY-101 Reveals Novel Insights Into IL-8-Driven Inflammation in COVID-19.Immunology · 2025Article
- Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers.Molecular medicine (Cambridge, Mass.) · 2025Article
- Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps-Fibroblast Crosstalk.European journal of immunology · 2025Article
- Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene.Experimental and therapeutic medicine · 2025Article
- Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps-Fibroblast Crosstalk.European journal of immunology · 2025Article
- Pharmacological mechanism of action of Lianhua Qingwen in the treatment of COVID-19 and facial neuritis.World journal of otorhinolaryngology - head and neck surgery · 2025Article
- Pathophysiological mechanisms of ARDS: a narrative review from molecular to organ-level perspectives.Respiratory research · 2025Review
- Neutrophils Display Novel Partners of Cytosolic Proliferating Cell Nuclear Antigen Involved in Interferon Response in COVID-19 Patients.Journal of innate immunity · 2025Article
- The diagnostic value of C-X-C motif chemokine 8 in elderly patients with bacterial upper respiratory tract infections and its correlation with prognosis.Frontiers in medicine · 2025Article
- The endothelial-immunothrombotic storm in viral sepsis: lessons from COVID-19.Frontiers in immunology · 2025Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophils provide a critical line of defense in immune responses to various pathogens, inflicting self-damage upon transition to a hyperactivated, procoagulant state. Recent work has highlighted proinflammatory neutrophil phenotypes contributing to lung injury and acute respiratory distress syndrome (ARDS) in patients with coronavirus disease 2019 (COVID-19). Here, we use state-of-the art mass spectrometry-based proteomics and transcriptomic and correlative analyses as well as functional in vitro and in vivo studies to dissect how neutrophils contribute to the progression to severe COVID-19. We identify a reinforcing loop of both systemic and neutrophil intrinsic IL-8 (CXCL8/IL-8) dysregulation, which initiates and perpetuates neutrophil-driven immunopathology. This positive feedback loop of systemic and neutrophil autocrine IL-8 production leads to an activated, prothrombotic neutrophil phenotype characterized by degranulation and neutrophil extracellular trap (NET) formation. In severe COVID-19, neutrophils directly initiate the coagulation and complement cascade, highlighting a link to the immunothrombotic state observed in these patients. Targeting the IL-8-CXCR-1/-2 axis interferes with this vicious cycle and attenuates neutrophil activation, degranulation, NETosis, and IL-8 release. Finally, we show that blocking IL-8-like signaling reduces severe acute respiratory distress syndrome of coronavirus 2 (SARS-CoV-2) spike protein-induced, human ACE2-dependent pulmonary microthrombosis in mice. In summary, our data provide comprehensive insights into the activation mechanisms of neutrophils in COVID-19 and uncover a self-sustaining neutrophil-IL-8 axis as a promising therapeutic target in severe SARS-CoV-2 infection.
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Registered trials
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.