Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study

OBJECTIVES: Coronavirus disease 2019 (COVID-19) results in severe inflammation at the acute stage. Chronic neuroinflammation and abnormal immunological response have been suggested to be the contributors to neuro-long-COVID, but direct evidence has been scarce. This study aims to determine the integrity of the blood-brain barrier (BBB) in COVID-19 intensive care unit (ICU) survivors using a novel MRI technique. METHODS: COVID-19 ICU survivors (n=7) and age and sex-matched control participants (n=17) were recruited from June 2021 to March 2023. None of the control participants were hospitalized due to COVID-19 infection. The COVID-19 ICU survivors were studied at 98.6 ± 14.9 days after their discharge from ICU. A non-invasive MRI technique was used to assess the BBB permeability to water molecules, in terms of permeability surface area-product (PS) in the units of mL/100 g/min. RESULTS: PS was significantly higher in COVID-19 ICU survivors (p=0.038) when compared to the controls, with values of 153.1 ± 20.9 mL/100 g/min and 132.5 ± 20.7 mL/100 g/min, respectively. In contrast, there were no significant differences in whole-brain cerebral blood flow (p=0.649) or brain volume (p=0.471) between the groups. CONCLUSIONS: There is preliminary evidence of a chronic BBB breakdown in COVID-19 survivors who had a severe acute infection, suggesting a plausible contributor to neurological long-COVID symptoms.