LOCOMOTIVE study

<b>Abstract</b>Although brain alterations may occur in post-acute sequelae of SARS-CoV-2 (PASC), their universality and link to neurodegeneration remain unclear. Here, we analyzed blood proteins and brain magnetic resonance imaging in individuals who experienced mild COVID-19 about a year prior, categorized into three groups: Cog-PASC (with cognitive impairment), Other-PASC (without cognitive impairment), and non-PASC controls. The Cog-PASC group showed elevated blood levels of astroglial damage-associated protein, reduced cingulate and insular cortical thickness, and increased paramagnetic susceptibility, indicating iron deposition, particularly in the cingulate cortex and hippocampus. We demonstrated increased choroid plexus volume in Cog-PASC compared to Other-PASC patients, associated with neuronal/astroglial damage, cortical thinning, and iron deposition. Blood proteomic analysis showed significantly altered proteins involved in oxidative stress responses and synaptic function in Cog-PASC patients, linked to neurodegenerative pathways. These findings suggest distinct neurodegenerative processes in Cog-PASC that are not observed in other PASC subtypes, even after mild COVID-19 infection.<br><b>Data collection</b>Data collection for follow-up clinical, imaging, and blood analyses has been completed for this study. This preliminary study aimed to investigate brain MRI and blood proteomics of the discovery cohort to assess whether patients exhibit distinct brain damage, structural alteration, and neurodegenerative processes primarily at the baseline following SARS-CoV-2 infection. Brain MRI scans are performed at baseline and after 1 year, primarily to assess longitudinal structural changes in the brain, including grey matter alterations. Blood samples are collected at baseline, 6 months, and 1 year, while symptom evaluation questionnaires are administered every 3 months.- Cognitive Assessments: Conducted using the Montreal Cognitive Assessment (MoCA), FAS, and PASC symptom scores.- Biological Samples: Serum and plasma samples were collected for proteomic analysis using the Olink 3,072 Explore using Proximity Extension Assay (PEA) technology and SIMOA (Single Molecule Array) HD-X platform.- Imaging: Brain MRI analysis for cortical parcellation, paramagnetic susceptibility, choroid plexus segmentation, and diffusion tensor imaging along perivascular spaces (DTI-ALPS) were performed at baseline to detect structural brain changes.