tetano
Editor, Senior Moderator
Respir Res
. 2025 Jun 11;26(1):213.
doi: 10.1186/s12931-025-03180-2. Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis
Georgios Divolis[SUP] #[/SUP][SUP] 1 [/SUP], Evgenia Synolaki[SUP] 2 [/SUP], Rodoula Tringidou[SUP] 3 [/SUP], Argyrios Tzouvelekis[SUP] 4 [/SUP], Dimitrios T Boumpas[SUP] 2 5 [/SUP], Panagiotis Skendros[SUP] 6 7 [/SUP], Ioanna-Evdokia Galani[SUP] #[/SUP][SUP] 8 [/SUP]
Affiliations
Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease linked with deregulated immune responses, leading to hyperinflammation, acute respiratory distress syndrome, and pulmonary fibrosis, often with fatal outcomes. Neutrophils play a central role in COVID-19 pathogenesis, with elevated peripheral blood neutrophil counts correlating with disease severity. Despite extensive research, the molecular processes associated with neutrophil hyperactivation in COVID-19 remain elusive.
Methods: To investigate the molecular signatures underlying neutrophil-driven pathology, we conducted transcriptome analysis in neutrophils isolated from the peripheral blood of COVID-19 patients versus healthy individuals. To evaluate the specificity of identified neutrophil signatures in COVID-19, we extended our transcriptomic analysis to neutrophils from patients with idiopathic pulmonary fibrosis (IPF), a non-infectious fibrotic lung disease. Additionally, immunofluorescence staining was performed on lung biopsy specimens from IPF patients to validate transcriptomic findings at the tissue level.
Results: Our analysis revealed significant transcriptional changes in COVID-19 neutrophils, particularly in pathways involved in immune regulation, inflammation, and antiviral responses. Additionally, pathways associated with autophagy and chromatin remodeling were upregulated, while translation-related processes were suppressed, indicating an increased predisposition for neutrophil extracellular trap (NET) release. This neutrophil transcriptional signature in COVID-19 appears to be associated with the previously reported deregulation of the Activin/Follistatin system in the periphery. Notably, a comparative transcriptomic analysis with neutrophils isolated from IPF patients revealed the induction of substantially overlapping inflammatory processes, suggesting common deregulated responses in COVID-19 and IPF. Consistently, significant NET formation, a hallmark of COVID-19-related inflammation, was observed within lung biopsies from IPF patients.
Conclusion: By delineating both shared and disease-specific molecular pathways, our findings validate the critical role of neutrophils in COVID-19 and IPF pathophysiology, highlighting their involvement in balancing the inflammatory response across diverse lung diseases.
Keywords: Activin; COVID-19; Follistatin; Idiopathic pulmonary fibrosis; Lung inflammation; NETosis; Neutrophils; RNA Sequencing; Transcriptomics; Viral infection.
. 2025 Jun 11;26(1):213.
doi: 10.1186/s12931-025-03180-2. Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis
Georgios Divolis[SUP] #[/SUP][SUP] 1 [/SUP], Evgenia Synolaki[SUP] 2 [/SUP], Rodoula Tringidou[SUP] 3 [/SUP], Argyrios Tzouvelekis[SUP] 4 [/SUP], Dimitrios T Boumpas[SUP] 2 5 [/SUP], Panagiotis Skendros[SUP] 6 7 [/SUP], Ioanna-Evdokia Galani[SUP] #[/SUP][SUP] 8 [/SUP]
Affiliations
- PMID: 40500689
- DOI: 10.1186/s12931-025-03180-2
Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease linked with deregulated immune responses, leading to hyperinflammation, acute respiratory distress syndrome, and pulmonary fibrosis, often with fatal outcomes. Neutrophils play a central role in COVID-19 pathogenesis, with elevated peripheral blood neutrophil counts correlating with disease severity. Despite extensive research, the molecular processes associated with neutrophil hyperactivation in COVID-19 remain elusive.
Methods: To investigate the molecular signatures underlying neutrophil-driven pathology, we conducted transcriptome analysis in neutrophils isolated from the peripheral blood of COVID-19 patients versus healthy individuals. To evaluate the specificity of identified neutrophil signatures in COVID-19, we extended our transcriptomic analysis to neutrophils from patients with idiopathic pulmonary fibrosis (IPF), a non-infectious fibrotic lung disease. Additionally, immunofluorescence staining was performed on lung biopsy specimens from IPF patients to validate transcriptomic findings at the tissue level.
Results: Our analysis revealed significant transcriptional changes in COVID-19 neutrophils, particularly in pathways involved in immune regulation, inflammation, and antiviral responses. Additionally, pathways associated with autophagy and chromatin remodeling were upregulated, while translation-related processes were suppressed, indicating an increased predisposition for neutrophil extracellular trap (NET) release. This neutrophil transcriptional signature in COVID-19 appears to be associated with the previously reported deregulation of the Activin/Follistatin system in the periphery. Notably, a comparative transcriptomic analysis with neutrophils isolated from IPF patients revealed the induction of substantially overlapping inflammatory processes, suggesting common deregulated responses in COVID-19 and IPF. Consistently, significant NET formation, a hallmark of COVID-19-related inflammation, was observed within lung biopsies from IPF patients.
Conclusion: By delineating both shared and disease-specific molecular pathways, our findings validate the critical role of neutrophils in COVID-19 and IPF pathophysiology, highlighting their involvement in balancing the inflammatory response across diverse lung diseases.
Keywords: Activin; COVID-19; Follistatin; Idiopathic pulmonary fibrosis; Lung inflammation; NETosis; Neutrophils; RNA Sequencing; Transcriptomics; Viral infection.