MRI Shows Brain Changes in People With Post COVID Symptoms

A new study in Nature Communications reports that people experiencing persistent cognitive impairment after COVID-19 exhibit measurable, biologically distinct changes in the brain.

The researchers used MRI, blood biomarkers, and proteomic profiling to examine a subgroup of the study identified as having cognitive impairment in post-acute sequelae of COVID-19 (referred to as Cog PASC).

This group showed neuroinflammatory and neurodegenerative patterns that did not appear in people with PASC who did not report cognitive symptoms or in recovered controls. Participants classified as Cog PASC had higher levels of GFAP and NfL, proteins that increase during astroglial and neuronal injury. MRI scans revealed more pronounced cortical thinning in the cingulate and insular regions, along with increased iron accumulation and an enlarged choroid plexus.

These features may reflect ongoing immune activation within the central nervous system.

Proteomic analyses also showed disruptions in pathways related to oxidative stress, mitochondrial activity, and synaptic function, providing possible explanations for the persistent brain fog experienced by many after mild COVID-19. The findings were validated in independent cohorts, which strengthens confidence in the observed biological pattern. While the cross-sectional design limits conclusions about cause and effect, the study underscores the need for targeted research and interventions for individuals facing long-term cognitive symptoms after COVID-19.

Citation

Knopman, D. S., Koltai, D., Laskowitz, D., Becker, J., Charvet, L., Wisnivesky, J., Federman, A., Silverstein, A., Lokhnygina, Y., Pilloni, G., Haddad, M., Mahncke, H., Van Vleet, T., Huang, R., Cox, W., Terry, D., Karwowski, J., McCray, N., Lin, J. J., McComsey, G. A., … RECOVER-NEURO Clinical Trial Group (2025). Evaluation of Interventions for Cognitive Symptoms in Long COVID: A Randomized Clinical Trial. JAMA neurology, e254415. Advance online publication. https://doi.org/10.1001/jamaneurol.2025.4415