Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study, 2023, Shi et al.

Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study
Wen Shi; Dengrong Jiang; Hannah Rando; Shivalika Khanduja; Zixuan Lin; Kaisha Hazel; George Pottanat; Ebony Jones; Cuimei Xu; Doris Lin; Sevil Yasar; Sung-Min Cho; Hanzhang Lu

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.

Link | PDF (NeuroImmune Pharmacology and Therapeutics)

 

Prior paper — Non-contrast MR imaging of blood-brain barrier permeability to water (2018, Magnetic Resonance in Medicine)

 

Here, cerebral blood flow as assessed by MRI is with the patient supine, so dynamic orthostatic factors won't be represented. Cerebral blood (and CSF) flow supine vs upright has been looked at in healthy people, eg —

Postural effects on cerebral blood flow and autoregulation (2017, Physiological Reports)

Cerebrovascular reactivity and cerebral autoregulation are improved in the supine posture compared to upright in healthy men and women (2020, PLOS ONE)

Upright versus supine MRI: effects of body position on craniocervical CSF flow (2021, Fluids and Barriers of the CNS)

Both blood flow and CSF flow could be compared with MRI, supine vs upright in ME and LC. I think to date upright MRI has only been used to look at the craniocervical junction. I think Michael VanElzakker's current study is at 7T for increased resolution, which will be supine only with current technology. Tilt-table with cerebral NIRS and extra- / trans-cranial Doppler ultrasound has been much more straightforward to evaluate, eg van Campen et al.