Prominent clinical evidence has shown that coronavirus disease 2019 (COVID-19) could result in prothrombotic states, which could be manifested as venous thrombosis, arterial thrombosis, or microvascular thrombosis, any of which could lead to a negative prognosis. Clinical data suggest that elevated blood viscosity is probably linked to the frequent occurrence of thrombophilia in patients with COVID-19. However, the underlying mechanism causing hyperviscosity in COVID-19 is still elusive.
In a recent flow imaging cytometry study by researchers from Massachusetts General Hospital, the authors discovered different types of cell clusters from the blood samples of patients with COVID-19 and explored the association between the phenotype of circulating clusters with potential clinical outcomes. Inspired by this study, we performed computational simulations to investigate the dynamics of different types of circulating cell clusters, namely white blood cell (WBC) clusters, platelet clusters, and red blood cell clusters, over a range of shear flows and quantify their impact on the viscosity of the blood. The cover image for the September 20 issue of Biophysical Journal is a simulation snapshot of a circulating cell cluster that contains two white blood cells (blue-colored cells) traveling in a complex microvessel network reconstructed on the basis of in vivo observations of mouse mesentery. This simulation shows that this cell cluster could lead to a local obstruction of the blood flow at the bifurcation site.
In our study, we further show that the increased level of fibrinogen due to COVID-19 infection can promote the formation of red blood cell clusters when the shear rate of the blood flow is relatively low, thereby elevating the blood viscosity, a mechanism that also leads to an increase in viscosity in other blood diseases, such as type 2 diabetes mellitus. We also discovered that the presence of WBC clusters could aggravate the abnormalities of local blood rheology. In particular, the extent of elevation of the local blood viscosity is enlarged as the size of the WBC clusters grows.
Through our study as illustrated on this cover, we demonstrated that computational modeling can serve as a powerful tool for investigating the pathological alterations of biorheology of blood and exploring their connections to clinical manifestations in infectious diseases, such as COVID-19 in which the patients’ fresh blood samples may be limited for in vitro experimental investigations.
- Elahe Javadi, He Li, Ander Dorken Gallastegi, Galit H. Frydman, Safa Jamali, and George Em Karniadakis
The cover image was generated by Dr. He Li, Dr. Guansheng Li, and Dr. Shengze Cai.