期刊
CELL REPORTS MEDICINE
卷 3, 期 12, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.xcrm.2022.100833
关键词
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资金
- Ghent University Special Research Fund (BOF)
- VIB Grand Challenges program
- Partner Therapeutics
- Chan Zuckerberg Initiative (CZI) Covid atlas project [2020-216717]
- UGent Covid grant Covid-Track project (BOFCOV) [01C04620]
- FWO Covid grant Covid-Trace project [G0G4520N]
- Ghent University GOA project [01G02418]
- NIH [75N9301900065]
GM-CSF plays a crucial role in COVID-19, but excessive use may lead to inflammation. Inhalation of GM-CSF does not improve oxygenation parameters, but it enhances antiviral immune response, providing a theoretical basis for further testing of GM-CSF as a non-invasive treatment for COVID-19.
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).
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