Impaired microcirculation and tissue hypoxia as a possible mechanism in ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease that usually occurs after an infection, in some cases also in patients with late effects after COVID-19 (Long-COVID). The disease mechanism is still unknown, and we lack biomarkers and effective treatments. However, there is an increasing number of research reports documenting biological changes in ME/CFS patients, and recent findings suggest that limitations in the blood supply may be an important factor. Based on these findings, we have a hypothesis that tissue hypoxia due to reduced blood circulation in small blood vessels disrupts the cells' energy metabolism in the patients. To test this hypothesis, we will analyze biochemical signatures of hypoxia in blood samples from ME/CFS and Long-COVID patients, taken at rest or during physical testing. We will also look at changes in blood and blood vessel cells and small particles that they can release, which may reveal new details about the disease mechanism. Our project aims to pursue the mechanisms behind ME/CFS through hypothesis-driven investigations in patient samples and laboratory studies, using new approaches. We will search for indications of impaired microcirculation and tissue hypoxia that can be triggered in an effort-dependent manner. We will address research questions related to mechanisms in blood and blood vessels that may be responsible for reduced tissue perfusion. This will also include mechanisms that can link reduced microcirculation to specific changes in the immune system. The findings will be able to provide new insight into the mechanisms behind ME/CFS and Long-COVID, reveal new directions for future research, and provide new opportunities for the development of biomarkers and treatment. The project will involve collaboration with leading researchers with complementary expertise and resources in the area.