ArticleCell reports. Medicine2022
Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in Cell reports. Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04326920 (A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Sargramostim), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 4% 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.
A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Sargramostim (Leukine®) in Improving Oxygenation and Short- and Long-term Outcome of COVID-19 (Corona Virus Disease) Patients With Acute Hypoxic Respiratory Failure.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- Chitin Is a Potent Inducer of Type 2 Airway Inflammation Independent of Endogenous Chitinolytic Activity.Allergy · 2026Article
- Article
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Macrophage makeover extreme viral edition: mechanisms of immune subversion and therapeutic perspectives.The Journal of general virology · 2026Review
- Influenza A Virus after Radiotherapy Amplifies Lung Injury and Monocyte-derived Macrophage Responses.American journal of respiratory cell and molecular biology · 2026Article
- Recombinant GM-CSF drug evaluation review.Immunotherapy · 2025Review
- Exosomal miR-218 secreted from endothelial progenitor cells mitigates acute lung injury in sepsis mice by inhibiting HMGA1 in alveolar macrophages.Stem cell research & therapy · 2025Article
- Restoring resident tissue macrophages to combat aging and cancer.Nature aging · 2025Review
- Review
- Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation.eLife · 2025Article
- Article
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- Differences in glycolytic metabolism between tissue-resident alveolar macrophages and recruited lung macrophages.Frontiers in immunology · 2025Review
- The role of alveolar macrophages in viral respiratory infections and their therapeutic implications.Biochemistry and biophysics reports · 2024Review
- Repeated inhalation of GM-CSF by nonhuman primates induces bronchus-associated lymphoid tissue along the lower respiratory tract.Respiratory research · 2024Article
- Recruited atypical Ly6GScience immunology · 2024Article
- The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Downregulation of IRF8 in alveolar macrophages by G-CSF promotes metastatic tumor progression.iScience · 2024Article
- Inhaled GM-CSF administered during ongoing pneumovirus infection alters myeloid and CD8 T cell immunity without affecting disease outcome.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 8 institutions in 2 countries.
Cedric BosteelsLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Karel F A Van DammeLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Elisabeth De LeeuwLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Jozefien DeclercqLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Bastiaan MaesLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Victor BosteelsDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium; Laboratory of ER Stress and Inflammation, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium.
Levi HosteDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Primary Immunodeficiency Research Lab, Faculty of Medicine and Health Sciences, Ghent University, Ghent 9000, Belgium.
Leslie NaesensDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Primary Immunodeficiency Research Lab, Faculty of Medicine and Health Sciences, Ghent University, Ghent 9000, Belgium.
Nincy DebeufLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Julie DeckersLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Basiel ColeDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
Marion PardonsDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
Daniela WeiskopfCenter for Autoimmunity and Inflammation and Center for Infectious Diseases and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Alessandro SetteCenter for Autoimmunity and Inflammation and Center for Infectious Diseases and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Yannick Vande WeygaerdeDepartment of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Thomas MalfaitDepartment of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Stefaan J VandecasteeleDepartment of Infectious Diseases, AZ Sint-Jan Brugge-Oostende, 8000 Brugge, Belgium.
Ingel K DemedtsDepartment of Pulmonary Medicine, AZ Delta General Hospital, 8800 Roeselare, Belgium.
Hans SlabbynckDepartment of Pulmonary Medicine, ZNA General Hospital, 2000 Antwerp, Belgium.
Sabine AllardDepartment of Internal Medicine, Universitair Ziekenhuis Brussel, 1000 Brussels, Belgium.
Pieter DepuydtDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Intensive Care Unit, Ghent University Hospital, 9000 Ghent, Belgium.
Eva Van BraeckelDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Jozefien De ClercqDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Infectious Diseases, Ghent University Hospital, 9000 Ghent, Belgium.
Liesbet MartensLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9000 Ghent, Belgium.
Sam DupontLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Ruth SeurinckData Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, 9000 Ghent, Belgium.
Niels VandammeData Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium; VIB Single Cell Core, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium.
Filomeen HaerynckDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Primary Immunodeficiency Research Lab, Faculty of Medicine and Health Sciences, Ghent University, Ghent 9000, Belgium.
Debasish F RoychowdhuryPartner Therapeutics, Inc., Lexington, MA 02421, USA.
Linos VandekerckhoveDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Infectious Diseases, Ghent University Hospital, 9000 Ghent, Belgium.
Martin GuilliamsLaboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9000 Ghent, Belgium.
Simon J TavernierDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Primary Immunodeficiency Research Lab, Faculty of Medicine and Health Sciences, Ghent University, Ghent 9000, Belgium; Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9000 Ghent, Belgium; Laboratory of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, 9000 Ghent, Belgium.
Bart N LambrechtLaboratory of Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent University, 9000 Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium. Electronic address: bart.lambrecht@ugent.be.
Ghent University · BEGhent University Hospital · BEVIB-UGent Center for Inflammation Research · BELa Jolla Institute for Immunology · USAZ Delta · BEAZ Sint-Jan · BEUniversitair Ziekenhuis Brussel · BEZiekenhuisnetwerk Antwerpen Stuivenberg · BE
Funding
No grant is acknowledged in the PubMed record.
Abstract
GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22).
Indexed as
COVID-19Macrophages, AlveolarGranulocyte-Macrophage Colony-Stimulating FactorHumansLungMacrophagesGranulocyte-Macrophage Colony-Stimulating Factoralveolar macrophageCITE-seqCOVID-19GM-CSFleukineoxygenationRCTsargramostimSARPACvirus
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
NCT04326920ClinicalTrials.gov
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.