Nature communicationsNov 26, 2025

Specific brain changes and nerve cell damage linked to thinking problems after long COVID

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Cognitive PASC was linked to reproducible brain MRI and blood-protein changes associated with neurodegeneration.

Evidence

This multi-cohort observational MRI and blood-proteomics analysis compared individuals about one year after mild COVID-19 with , , and non-PASC controls across exploration, matched, and validation cohorts.

Caveat

The imaging and proteomic associations do not prove that mild COVID-19 caused progressive neurodegeneration.

Simplified

Although brain alterations have been reported in post-acute sequelae of SARS-CoV-2 (PASC), their prevalence and relationship to neurodegeneration remain unclear. We analyzed blood proteins and brain MRI from individuals approximately one year after mild COVID-19, categorized as (with cognitive impairment), (without cognitive impairment), or non-PASC controls, across exploration, covariate-matched, and independent validation cohorts. In the exploration cohort, Cog-PASC showed elevated astroglial damage-associated proteins and structural and microstructural alterations across multiple cortical and subcortical regions, including cortical thinning in the cingulate and insular cortices, increased paramagnetic susceptibility in the hippocampus, and enlarged choroid plexus volume. In the age-, sex-, and education-matched cohort, cortical thinning and increased susceptibility in the cingulate remained significant. Blood proteomics revealed broader alterations involving oxidative stress responses and synaptic function in Cog-PASC, linked to neurodegenerative pathways. In the validation cohort, increased neuronal and astroglial damage-associated proteins, cortical thinning in the cingulate and insular cortices, and increased hippocampal susceptibility were demonstrated, along with enlarged choroid plexus, confirming the reproducibility of these neurodegeneration-associated alterations. These findings suggest distinct neurodegenerative processes in Cog-PASC not observed in other-PASC subtypes, even after mild COVID-19 infection.

Key numbers

2.4183 mm

Cortical Thinning

in group.

Higher in vs.

Increased Choroid Plexus Volume

comparison.

Differentially Expressed Proteins

Comparison of blood proteins between and .

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Specific brain changes and nerve cell damage linked to thinking problems after long COVID

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