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

doi:10.1515/nipt-2023-0018

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

NeuroImmune Pharm Ther. 2023 Nov 22;2(4):333-338. doi: 10.1515/nipt-2023-0018. eCollection 2023 Dec.

Authors

Wen Shi^{1

2}, Dengrong Jiang², Hannah Rando³, Shivalika Khanduja³, Zixuan Lin², Kaisha Hazel², George Pottanat², Ebony Jones², Cuimei Xu², Doris Lin², Sevil Yasar⁴, Sung-Min Cho⁵, Hanzhang Lu^{1

2

6}

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² The Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Neurology, Neurosurgery, Surgery, Anesthesiology, and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA.

Abstract

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.

Keywords: COVID-19; MRI; WEPCAST; blood-brain barrier; permeability.

Abstract

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