ORCID
https://orcid.org/0000-0002-3817-3658
Full-time or Part-time Study
Full-time
Level
Postgraduate
Presentation Type
Poster
Abstract
Background
Venous thromboembolism (VTE) is a high-incidence complication of severe SARS-CoV-2-associated COVID-19. Recently, abnormal tissue factor expression has been linked to thromboembolic events in patients with COVID-19. Monocytes and macrophages are the predominant source of tissue factor in peripheral circulation, which suggests a potential pathomechanistic interplay between SARS-CoV-2 and the monocyte-macrophage axis. However, the link between monocytes and macrophages and the thromboembolic risk associated with COVID-19 is largely unaddressed.
Aims
In this study, we investigated changes in monocyte/macrophage procoagulant activity in response to the SARS-CoV-2 spike protein.
Methods
Immortalised human-derived monocytes and differentiated macrophages were treated with the SARS-CoV-2 spike protein, and changes in monocyte/macrophage procoagulant activity were assessed using biochemical and haematological assays.
Results
The ancestral Wuhan-Hu-1 SARS-CoV-2 spike protein induced time- and concentration-dependent increases in monocyte/macrophage procoagulant activity, characterised by a significant reduction in the recalcified clotting time of human plasma. Moreover, monocyte/macrophage procoagulant activity correlated with the severity of the SARS-CoV-2 variant of concern. The resulting clots possessed features consistent with the prothrombotic phenotype: decreased permeability. increased fibrin inclusion, and increased resistance to fibrinolysis. Furthermore, spike protein-induced procoagulant activity was shown to require extrinsic coagulation factors; in particular, recalcified clotting times were significantly affected by deficiencies in tissue factor-factor VIIa complexes.
Conclusion
Collectively, our data suggests that the SARS-CoV-2 spike protein promotes tissue factor/factor VIIa-dependent procoagulant activity in monocytes and macrophages as a pathocontributor to the COVID-19-associated coagulopathy. Investigations are on-going to further understand the pathophysiological interplay between SARS-CoV-2 and the monocyte-macrophage axis in patients with COVID-19.
Keywords:
SARS-CoV-2, spike protein, COVID-19, tissue factor, biochemistry
Start Date
2-11-2023 11:15 AM
End Date
2-11-2023 12:00 PM
Recommended Citation
Harte, James, "Monocytes and Macrophages Promote Increased Tissue Factor-Factor VIIa-Dependent Procoagulant Activity in Response to the SARS-CoV-2 Spike Protein" (2023). ORBioM (Open Research BioSciences Meeting). 19.
https://sword.cit.ie/orbiom/2023/posters/19
Included in
Monocytes and Macrophages Promote Increased Tissue Factor-Factor VIIa-Dependent Procoagulant Activity in Response to the SARS-CoV-2 Spike Protein
Background
Venous thromboembolism (VTE) is a high-incidence complication of severe SARS-CoV-2-associated COVID-19. Recently, abnormal tissue factor expression has been linked to thromboembolic events in patients with COVID-19. Monocytes and macrophages are the predominant source of tissue factor in peripheral circulation, which suggests a potential pathomechanistic interplay between SARS-CoV-2 and the monocyte-macrophage axis. However, the link between monocytes and macrophages and the thromboembolic risk associated with COVID-19 is largely unaddressed.
Aims
In this study, we investigated changes in monocyte/macrophage procoagulant activity in response to the SARS-CoV-2 spike protein.
Methods
Immortalised human-derived monocytes and differentiated macrophages were treated with the SARS-CoV-2 spike protein, and changes in monocyte/macrophage procoagulant activity were assessed using biochemical and haematological assays.
Results
The ancestral Wuhan-Hu-1 SARS-CoV-2 spike protein induced time- and concentration-dependent increases in monocyte/macrophage procoagulant activity, characterised by a significant reduction in the recalcified clotting time of human plasma. Moreover, monocyte/macrophage procoagulant activity correlated with the severity of the SARS-CoV-2 variant of concern. The resulting clots possessed features consistent with the prothrombotic phenotype: decreased permeability. increased fibrin inclusion, and increased resistance to fibrinolysis. Furthermore, spike protein-induced procoagulant activity was shown to require extrinsic coagulation factors; in particular, recalcified clotting times were significantly affected by deficiencies in tissue factor-factor VIIa complexes.
Conclusion
Collectively, our data suggests that the SARS-CoV-2 spike protein promotes tissue factor/factor VIIa-dependent procoagulant activity in monocytes and macrophages as a pathocontributor to the COVID-19-associated coagulopathy. Investigations are on-going to further understand the pathophysiological interplay between SARS-CoV-2 and the monocyte-macrophage axis in patients with COVID-19.