CSF Inflammatory Markers Tied to Brain Alterations in SARS-CoV-2

Deborah L. Ungerleider, MD, for Medscape

March 04, 2022

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Cerebrospinal fluid (CSF) inflammatory marker levels were found to be associated with changes in gray matter volume and cortical thickness in the frontal, orbitofrontal, and temporal regions in hospitalized patients with severe SARS-CoV-2 infection who had different levels of neurologic involvement.

Why This Matters

  • Patients with severe SARS-CoV-2 infections have been shown to have chronic neuronal dysfunction secondary to a post-viral hyperinflammatory response.

  • The ability to measure clinical indicators of this inflammatory response and the affect of these infections on the brain structure may aid in future preventive and/or treatment measures.

Study Design

  • This was a prospective multicenter cross-sectional study that included patients aged 18 years or older with SARS-CoV-2 (confirmed by polymerase chain reaction) and neurologic symptoms who were treated at Basel University Hospital between August 2020 and April 2021.

  • The patients underwent 3D high-resolution T1-weighted MRI sequences of the entire brain. Anatomic T1wMPRAGE MRI sequences were acquired using two MRI scanners; cortical thickness and volumetric segmentation were performed with the FreeSurfer-6.0 image analysis suite.

  • The neurologic symptoms were classified as mild, moderate, or severe.

  • For a subgroup of patients, CSF studies were also conducted (leukocytes, lactate, protein levels, CSF blood/albumin ratio, and five cytokines [plasma-TRANCE, plasma-EN-RAGE, CSF-OPG, CSF-TRANCE, and CSF-EN-RAGE]. These cytokines have been associated with the severity of SARS-CoV-2 infection.)

  • The control group comprised age- and sex-matched healthy individuals with the same image protocol.

Key Results

  • Compared to the control patients, the study patients had lower cortical gray matter volume in the right rostral anterior cingulate, left medial orbitofrontal, and left superior frontal regions (P = .46).

  • There were no significant differences for cortical thickness or surface area between the patients with SARS-CoV-2 infection and the control patients.

  • There was a positive correlation between the CSF/blood-albumin ratio and the left rostral anterior cingulate (P = .03), left lateral orbitofrontal (P = .02), left pars triangularis (P = .02), left postcentral (P = .03), and right paracentral (P = .04) regional cortical thickness.

  • A positive correlation was found between EN-RAGE and the left pars triangularis (P = .002).

  • There was also a significant positive correlation for surface area between EN-RAGE and the right posterior cingulate cortex (P = .04).

  • The gray matter volume in the orbitofrontal area was negatively associated with CSF/blood-albumin ratio, protein levels, and CSF EN-RAGE.

  • CSF leukocytes were negatively associated with gray matter volume in the right lateral orbitofrontal and left inferior temporal regions (P = .03, for both).

  • CSF lactate was negatively associated with gray matter volume in the left inferior temporal (P = .02), left rostral middle frontal (P = .04), and right lateral orbitofrontal (P = .04) regions.


  • The authors did not report any study limitations.


  • The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, "Brain Cortical Changes Are Related to Inflammatory Biomarkers in Hospitalized SARS-CoV-2 Patients With Neurological Symptoms," written by Gretel Sanabria-Diaz, PhD, from Translational Imaging in Neurology (ThINK) Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, and colleagues, published on MedRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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