The importance of microvascular endothelial dysfunction for acute and long-term complications of COVID-19: clinical and mechanistic insights

Bakgrund:

Vascular injury leading to impaired tissue perfusion, organ failure and increased risk for thromboembolic events are common and serious complications contributing to morbidity and mortality in the acute setting of COVID-19. The underlying cause of the vascular injury remains unclear. The pathophysiology behind long COVID, which is a growing health problem to a large number of individuals, is completely unknown.

Observations suggest that the structure of red blood cells (RBC) is altered in COVID-19, and we recently discovered that altered RBC function in cardiovascular disease is an important factor contributing to cardiovascular injury via mechanism involving oxidative stress. Whether this mechanism is involved in in COVID-19 is not known.

Målsättning:

To test the hypothesis that microvascular endothelial dysfunction is an underlying cause of complications in the acute phase and in long COVID, and to identify key mechanism underlying the vascular injury. Specific aims are to: 1. Determine microvascular function in hospitalized patients with COVID-19 and in patients with long COVID

2. Identify the importance of RBC dysfunction as mediator of vascular injury in acute and long COVID

3. To identify the molecular pathways driving vascular injury in COVID and explore the effect of therapeutic interventions targeting these pathways Arbetsplan:

The study is performed on two cohorts of COVID patients and matched controls. Cohort 1 (n=20) are recruited during hospitalization for COVID and undergoes examination of peripheral endothelial function during hospitalization and at 4 and 9 months follow-up. Cohort 2 (n=25) consists of patients fulfilling criteria for long COVID.

They undergo examination of endothelial function as above and Doppler-based myocardial microvascular function 4-9 months after the acute infection. Blood samples are collected from both cohorts for identification of cellular and molecular mechanisms behind vascular injury with a focus on oxidative stress mediated by RBCs.

Betydelse:

The study will demonstrate the presence of microvascular endothelial dysfunction in patients with acute and long COVID, and give insights into the mechanisms driving the vascular injury. The project may lay the foundation for development of targeted therapeutic strategies to prevent these serious and long-lasting complications.