Abstract
Rational: Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics. Further insight into SARS-CoV-2 effects on neutrophil biology at the functional level could identify therapeutic targets to treat severe disease.
Objectives: Examine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC)
Methods: Isolated neutrophils from 41 non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured.
Results: Compared to AMC, COVID-19 neutrophils demonstrated elevated migration (p=0.0397) and NETosis (p=0.036), but impaired phagocytosis (p=0.023) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.022) on COVID-19 neutrophils. COVID-19 patients showed increased systemic markers of NETosis including cfDNA (p=0.015) and impaired DNAse activity (p<0.0.001). MPO, VEGF, sTNFRI, and IL-6 (p<0001) were elevated in COVID-19, which positively correlated with disease severity by 4C score.
Conclusion: Circulating neutrophils from COVID-19 patients display altered phenotype, elevated migration, impaired anti-microbial responses and elevated NETosis. Targeting neutrophil function may help modulate COVID-19 severity.
Objectives: Examine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC)
Methods: Isolated neutrophils from 41 non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured.
Results: Compared to AMC, COVID-19 neutrophils demonstrated elevated migration (p=0.0397) and NETosis (p=0.036), but impaired phagocytosis (p=0.023) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.022) on COVID-19 neutrophils. COVID-19 patients showed increased systemic markers of NETosis including cfDNA (p=0.015) and impaired DNAse activity (p<0.0.001). MPO, VEGF, sTNFRI, and IL-6 (p<0001) were elevated in COVID-19, which positively correlated with disease severity by 4C score.
Conclusion: Circulating neutrophils from COVID-19 patients display altered phenotype, elevated migration, impaired anti-microbial responses and elevated NETosis. Targeting neutrophil function may help modulate COVID-19 severity.
| Original language | English |
|---|---|
| Article number | OA3974 |
| Journal | European Respiratory Journal |
| Volume | 58 |
| Issue number | suppl 65 |
| DOIs | |
| Publication status | Published - 25 Nov 2021 |
| Event | ERS International Congress 2021 - Duration: 5 Sept 2021 → 8 Sept 2021 |