A computational study of fibrinogen-induced alteration in microvascular blood flow in COVID-19

Patients infected with COVID-19 may experience significant and long-lasting changes in the mechanical and rheological properties of their blood cells, leading to microvascular dysfunction and other vascular complications such as microthrombosis. In this study, we perform detailed computational simulations to investigate the fibrinogen-dependent changes in microvascular blood flow. First, we develop a coarse-grained molecular model of plasma fibrinogen to investigate the correlation between fibrinogen concentration and plasma viscosity. Our simulation results show that plasma viscosity increases exponentially with fibrinogen concentration. We then use a coarse-grained RBC model to quantify the fibrinogen-dependent aggregation strength of RBC doublets and compare it with available experimental results. Next, we probe the effect of fibrinogen concentration on COVID-19 blood viscosity. Our simulation results show that increased plasma viscosity and blood cell aggregation are responsible for elevated blood viscosity. Finally, we quantify the alterations in microvascular blood flow in response to changes in cell adhesion. We find that the recruitment of WBCs and platelets would slow blood flow. The WBC-platelet adhesive interaction exacerbates the blockages, forming a complete blood occlusion at relatively low blood velocities. As blood velocities increase, the larger clusters of blood cells occluded by cell adhesion are more likely to dislodge from the site of inflammation. This computational study advances our understanding of the complex cell-cell interactions that influence microvascular blood flow. It highlights the importance of fibrinogen-induced changes in plasma viscosity, blood cell aggregation and adhesion in the risk of microvascular complications in patients with COVID-19.

Automated summary

Patients with COVID-19 may experience changes in the mechanical and rheological properties of their blood cells, leading to microvascular dysfunction and other vascular complications. An increase in fibrinogen concentration is associated with elevated plasma viscosity, blood cell aggregation, and elevated blood viscosity. Changes in cell adhesion can affect microvascular blood flow, with the recruitment of white blood cells and platelets slowing down blood flow and potentially leading to complete blood occlusion.