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

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Abstract

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.

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The corresponding author’s data supporting this study’s findings are available upon reasonable request. This manuscript has data included as electronic supplementary material.

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Acknowledgements

This work was supported by the Zhejiang Provincial Natural Science Foundation of China (no. LY22A020004), and the Fundamental Research Funds for the Central Universities (no. 226-2022-00125). Simulations were conducted at the Beijing Super Cloud Computing Center (BLSC).

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Authors and Affiliations

  1. Department of Engineering Mechanics and Center for X-Mechanics, Zhejiang University, Hangzhou, 310027, China

    Keqin Han, Shuhao Ma, Shuo Wang, Xiaojing Qi & Xuejin Li

  2. Mathematics and Science College, Shanghai Normal University, Shanghai, 200234, China

    Wenwen Zhou & Ling Guo

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  1. Keqin Han
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  3. Shuhao Ma
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Contributions

KH: formal analysis, investigation, methodology, validation, writing—original draft, writing—review and editing, visualization. WZ: formal analysis, writing— review and editing. SM: formal analysis, methodology, writing—review and editing. SW: formal analysis, methodology, writing—review and editing. XQ: formal analysis, methodology, writing—review and editing. LG: conceptualization, supervision, writing—review and editing. XL: conceptualization, formal analysis, supervision, writing—original draft, writing—review and editing.

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Correspondence to Ling Guo or Xuejin Li.

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Han, K., Zhou, W., Ma, S. et al. A computational study of fibrinogen-induced alteration in microvascular blood flow in COVID-19. Eur. Phys. J. Spec. Top. 232, 2761–2772 (2023). https://doi.org/10.1140/epjs/s11734-023-00901-w

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