Summary:
COVID-19, caused by SARS-CoV-2, not only affects the respiratory system but also leads to neurological symptoms, such as ‘brain fog’. Some studies suggest that breakdown of the blood-brain barrier (BBB) may underlie these neurological manifestations. Postmortem analysis of COVID-19 patients’ brains reveals BBB disruption, yet the exact mechanisms, especially in cases of long COVID, remain unclear. This study explores how BBB breakdown may contribute to neurological symptoms in COVID-19 patients, particularly those with long COVID, and found that BBB disruption and systemic inflammation is evident in patients with COVID-19. This suggests that assessing BBB integrity could be a valuable biomarker and offer an approach to managing long COVID, and also that sustained systemic inflammation and persistent BBB dysfunction are key features of brain fog in long COVID.
Abstract:
Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.
Article Publication Date: 22/02/2024
DOI: 10.1038/s41593-024-01576-9
