The Impact of COVID-19 on Cellular Factors Influencing Red Blood Cell Aggregation Examined in Dextran: Possible Causes and Consequences

Abstract

Several studies have indicated that COVID-19 can lead to alterations in blood rheology, including an increase in red blood cell aggregation. The precise mechanisms behind this phenomenon are not yet fully comprehended. The latest findings suggest that erythrocyte aggregation significantly influences microcirculation, causes the formation of blood clots in blood vessels, and even damages the endothelial glycocalyx, leading to endothelial dysfunction. The focus of this research lies in investigating the cellular factors influencing these changes in aggregation and discussing potential causes and implications in the context of COVID-19 pathophysiology. For this purpose, the aggregation of erythrocytes in a group of 52 patients with COVID-19 pneumonia was examined in a 70 kDa Dextran solution, which eliminates the influence of plasma factors. Using image analysis, the velocities and sizes of the formed aggregates were investigated, determining their porosity. This study showed that the process of erythrocyte aggregation in COVID-19 patients, independent of plasma factors, leads to the formation of more compact, denser, three-dimensional aggregates. These aggregates may be less likely to disperse under circulatory shear stress, increasing the risk of thrombotic events. This study also suggests that cellular aggregation factors can be responsible for the thrombotic disorders observed long after infection, even when plasma factors have normalized. The results and subsequent broad discussion presented in this study can contribute to a better understanding of the potential complications associated with increased erythrocyte aggregation.

Keywords: COVID-19; blood rheology; pneumonia; porosity of aggregates; red blood cells aggregation.

Figure 1

The aggregate radius (r) and velocity (v) as a function of time for COVID-19 patients upon admission to hospital.

Figure 2

The peak aggregate radius for healthy subjects (H) and COVID-19 patients upon admission to hospital (0), after 1 week of hospitalization (1W), and 6 months after infection (6M). Values outside four and seven times the interquartile range were considered outliers and extremes, respectively. For significant differences between measurements or groups, the significance levels (p) for adjacent bars were shown.

Figure 3

The peak aggregate velocity for healthy subjects (H) and COVID-19 patients upon admission to hospital (0), after 1 week of hospitalization (1W), and 6 months after infection (6M). Values outside four and seven times the interquartile range were considered outliers and extremes, respectively. For significant differences between measurements or groups, the significance levels (p) for adjacent bars were shown.

Figure 4

The time to peak aggregate radius and velocity for healthy subjects (H) and COVID-19 patients at admission to hospital (0), after 1 week hospitalization (1W), and 6 months after infection (6M). Values outside 4 and 7 times the interquartile range were considered outliers and extremes, respectively.

Figure 5

The aggregate porosity for healthy subjects (H) and COVID-19 patients at admission to hospital (0), after 1 week hospitalization (1W), and 6 months after infection (6M). Values outside four times the interquartile range were considered outliers. For significant differences between measurements or groups, the significance levels (p) for adjacent bars were shown.

Figure 6

The consecutive images of red blood cell suspension (top) and the image time sequence composed from them (bottom) for COVID-19 patients upon admission to hospital.