Platelets are essential for hemostasis (a process that stops bleeding), but also play an important role in the regulation of inflammation. Activation of platelets requires energy, which can be generated by metabolism of substrates such as glucose and lipids within platelets. This project aimed to determine the role of energy metabolism in platelets in their function during pneumonia. The investigations were roughly divided in two parts: observational studies in patients with pneumonia, and experimental (pneumonia) studies in mice with deficiencies of key metabolic mediators specifically in platelets.
This project started in the midst of the COVID-19 pandemic, a disease that had not yet emerged during the application process. We saw this as an opportunity considering that COVID-19 represents a new type of pneumonia. We detected a strong defect in the energy metabolism of platelets from COVID-19 patients resulting from a profound dysfunction of mitochondria (small structures within cells that are important for energy generation) and associated with a reduced platelet responsiveness. We also found strong differences in the lipid composition of platelets from patients with COVID-19 relative to controls. Remarkably, platelets from COVID-19 patients released more bioactive proteins implicated in inflammation and thrombosis, than platelets from patients with “regular” pneumonia. Platelets from mice with platelet-specific deficiencies in metabolic mediators showed altered functions in laboratory studies; however, during experimentally induced pneumonia these mice were not different from control mice, indicating that the mediators studied are not important during infection of the airways.
Overall, this project generated novel information on energy metabolism and lipid composition of platelets in COVID-19 and pneumonia, which is important for our understanding of platelet function in hemostasis and inflammation.