Circulating cellular clusters are associated with thrombotic complications and clinical outcomes in COVID-19

Dorken-Gallastegi, Ander; Lee, Yao; Li, Guansheng; Li, He; Naar, Leon; Li, Xuejin; Ye, Ting; Cott, Elizabeth Van; Rosovsky, Rachel; Gregory, D. W.; Tompkins, Ronald G.; Karniadakis, George; Kaafarani, Haytham; Velmahos, George C.; Lee, Jarone; Frydman, Galit H.

doi:10.1016/j.isci.2023.107202

Cited by 8 publications

(8 citation statements)

References 58 publications

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“…Interestingly, in one of the first studies, an increase in phosphatidylserine-positive platelet vesicles was observed in patients with moderate form [39]. Other work indicates that an increased volume and level of activation of platelet integrins are positively correlated with disease severity [40,68,71]; an association has also been reported for levels of circulating aggregates with complications or disease severity [70,72]. Interestingly, the previously cited work [49] found the virus in the platelets of almost all non-survivors but not the survivors.…”

Section: How Sars-cov-2 Affects Plateletsmentioning

confidence: 88%

“…Some of these activation markers overlap with the markers of apoptosis, which is not always easy to differentiate [46]. Numerous platelet aggregates with neutrophils, monocytes, and T cells are regularly detected in the blood of patients [45,67,70,[72][73][74]. Thrombocytopenia with COVID-19 is not necessary but is quite common [75].…”

Section: How Sars-cov-2 Affects Plateletsmentioning

confidence: 99%

“…Going back to the more reliable aspects, systematic changes in platelet function in COVID-19 can be considered well established. The researchers generally agree that thrombocytopenia is common but not severe (unless ECMO is used) and that platelets circulate in a pre-activated state, with at least some of them in an "over-activated" procoagulant (necrotic) state [39,40,45,[66][67][68][69][70][71], and some in aggregates with other cells [45,67,70,[72][73][74].…”

Section: Problems and Their Statusmentioning

confidence: 99%

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The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19

Panteleev,

Sveshnikova,

Shakhidzhanov

et al. 2023

IJMS

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The hematological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important in COVID-19 pathophysiology. However, the interactions of SARS-CoV-2 with platelets and red blood cells are still poorly understood. There are conflicting data regarding the mechanisms and significance of these interactions. The aim of this review is to put together available data and discuss hypotheses, the known and suspected effects of the virus on these blood cells, their pathophysiological and diagnostic significance, and the potential role of platelets and red blood cells in the virus’s transport, propagation, and clearance by the immune system. We pay particular attention to the mutual activation of platelets, the immune system, the endothelium, and blood coagulation and how this changes with the evolution of SARS-CoV-2. There is now convincing evidence that platelets, along with platelet and erythroid precursors (but not mature erythrocytes), are frequently infected by SARS-CoV-2 and functionally changed. The mechanisms of infection of these cells and their role are not yet entirely clear. Still, the changes in platelets and red blood cells in COVID-19 are significantly associated with disease severity and are likely to have prognostic and pathophysiological significance in the development of thrombotic and pulmonary complications.

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Section: How Sars-cov-2 Affects Plateletsmentioning

confidence: 88%

Section: How Sars-cov-2 Affects Plateletsmentioning

confidence: 99%

Section: Problems and Their Statusmentioning

confidence: 99%

See 1 more Smart Citation

The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19

Panteleev,

Sveshnikova,

Shakhidzhanov

et al. 2023

IJMS

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show abstract

“…DPD is a mesoscopic particle-based simulation technique, where each DPD particle represents an aggregate of molecules interacting with others through soft pairwise forces [36,37]. This method accurately captures the hydrodynamic behavior of fluids at the mesoscale and has proven successful in investigating complex fluid systems [38,21,39,40]. The evolution of computational capabilities in the past two decades has fostered the advancement and application of multiscale biophysical models for RBCs.…”

Section: Dpd Methods and Multiscale Blood Cell Modelsmentioning

confidence: 99%

“…This includes models operating at the protein level [41, 42, 43, 44, 45, 46, 47, 48, 49] and cellular level [ ? 44, 50, 51, 52, 53, 54, 55, 56, 57, 40, 58]. While protein-level RBC models can simulate pathological alterations in RBC membrane structure associated with blood disorders, their application to modeling blood cell suspensions or blood flow is hindered by computational costs.…”

Section: Methods and Modelsmentioning

confidence: 99%

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

Li,

Ndou

et al. 2024

Preprint

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The spleen constantly clears altered red blood cells (RBCs) from the circulation, tuning the balance between RBC formation (erythropoiesis) and removal. The retention and elimination of RBCs occur predominantly in the open circulation of the spleen, where RBCs must cross submicron-wide inter-endothelial slits (IES). Several experimental and computational studies have illustrated the role of IES in filtrating the biomechanically and morphologically altered RBCs based on a rigid wall assumption. However, these studies also reported that when the size of IES is close to the lower end of clinically observed sizes (less than 0.5μm), an unphysiologically large pressure difference across the IES is required to drive the passage of normal RBCs, sparking debates on the feasibility of the rigid wall assumption. In this work, we perform a computational investigation based on dissipative particle dynamics (DPD) to explore the impact of the deformability of IES on the filtration function of the spleen. We simulate two deformable IES models, namely the passive model and the active model. In the passive model, we implement the worm-like string model to depict the IES’s deformation as it interacts with blood plasma and allows RBC to traverse. In contrast, the active model involved regulating the IES deformation based on the local pressure surrounding the slit. To demonstrate the validity of the deformable model, we simulate the filtration of RBCs with varied size and stiffness by IES under three scenarios: 1) a single RBC traversing a single slit; 2) a suspension of RBCs traversing an array of slits, mimickingin vitrospleen-on-a-chip experiments; 3) RBC suspension passing through the 3D spleen filtration unit known as ‘the splenon’. Our simulation results of RBC passing through a single slit show that the deformable IES model offers more accurate predictions of the critical cell surface area to volume ratio that dictate the removal of aged RBCs from circulation compared to prior rigid-wall models. Our biophysical models of the spleen-on-a-chip indicates a hierarchy of filtration function stringency: rigid model > passive model > active model, providing a possible explanation of why the spleen-on-a-chip could overestimate the filtration function of IES. We also illustrate that the biophysical model of ‘the splenon’ enables us to replicate theex vivoexperiments involving spleen filtration of malaria-infected RBCs. Taken together, our simulation findings indicate that the deformable IES model could serve as a mesoscopic representation of spleen filtration function closer to physiological reality, addressing questions beyond the scope of current experimental and computational models and enhancing our understanding of the fundamental flow dynamics and mechanical clearance processes within in the human spleen.

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Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

Li,

Ndour

et al. 2024

Computers in Biology and Medicine

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Circulating cellular clusters are associated with thrombotic complications and clinical outcomes in COVID-19

Cited by 8 publications

References 58 publications

The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19

The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

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