The Impact of COVID on the Brain

Background

Understanding the impacts of COVID on the brain is an urgent scientific challenge with short and long-term implications for Irish healthcare and the broader social welfare system. FutureNeuro teams reacted nimbly to the opportunity presented by the establishment of national biobanks and longitudinal-tracked patient cohorts during the pandemic to make important breakthroughs on the mechanism causing long COVID. Here, we report that the network of small blood vessels in the human brain is disrupted in patients with long COVID and brain fog (cognitive impairment).

Breakthrough

Vascular disruption has been implicated in COVID-19 pathogenesis and may predispose to the neurological sequelae associated with Long COVID. Yet, it remains unclear how blood-brain barrier (BBB) function is affected in long COVID. In a collaborative effort, our Principal Investigators Prof Matt Campbell and Prof Colin Doherty, alongside colleagues, unveiled a significant breakthrough. They discovered that BBB disruption is not only evident during acute infection with SARS-CoV-2 but persists in long COVID patients experiencing brain fog.

Using dynamic contrast-enhanced MRI, they showed a correlation between BBB disruption and changes in brain volume. The analysis of gene expression revealed dysregulation in the coagulation system and a dampened adaptive immune response in individuals with brain fog. In vitro experiments revealed an increase in adhesion of peripheral blood mononuclear cells to human brain endothelial cells, and exposure of endothelial cells to serum from long COVID patients induced the expression of inflammatory markers. The findings suggest that sustained systemic inflammation and persistent, localised BBB dysfunction is a key feature of long COVID-associated brain fog.

Potential impact

By pinpointing damage to the blood vessels in the brain, we may now be able to develop targeted therapies for individuals experiencing the long-term effects of COVID. It is our vision that targeted regulation of the blood brain barrier (BBB) will change the landscape of how neurological disorders are treated in the future. Read more about this research, published in the Journal of Nature Neuroscience.