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.

<b>摘要</b>尽管严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后急性后遗症（Post-acute sequelae of SARS-CoV-2, PASC）可出现脑部改变，但其普遍性及与神经退行性变的关联仍有待阐明。本研究对约1年前罹患轻型新型冠状病毒肺炎（COVID-19）的受试者开展血液蛋白质组与脑部磁共振成像（magnetic resonance imaging, MRI）分析，将其分为三组：认知障碍型PASC（Cog-PASC，伴认知功能损害）、非认知障碍型PASC（Other-PASC，无认知功能损害）及非PASC对照组。认知障碍型PASC组受试者的血液中星形胶质细胞损伤相关蛋白水平升高，扣带回与岛叶皮层厚度降低，顺磁磁化率升高，提示存在铁沉积，尤以扣带回皮层与海马体为著。本研究发现，相较于非认知障碍型PASC患者，认知障碍型PASC组的脉络丛体积增大，且该改变与神经元/星形胶质细胞损伤、皮层变薄及铁沉积密切相关。血液蛋白质组分析显示，认知障碍型PASC患者体内参与氧化应激应答与突触功能的蛋白质水平发生显著改变，且这些改变与神经退行性通路相关。上述结果表明，即使在轻型新型冠状病毒肺炎感染后，认知障碍型PASC仍存在独特的神经退行性过程，而该过程在其他PASC亚型中并未出现。<br><b>数据采集</b>本研究的随访临床、影像学及血液分析数据采集工作已全部完成。本项预实验旨在对发现队列开展脑部磁共振成像与血液蛋白质组学分析，以评估受试者在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后的基线阶段是否存在独特的脑损伤、结构改变及神经退行性过程。分别于基线与感染后1年进行脑部磁共振成像扫描，主要用于评估脑部的纵向结构变化，包括灰质改变。血液样本分别于基线、感染后6个月及1年采集，同时每3个月开展一次症状评估问卷调研。- 认知评估：采用蒙特利尔认知评估量表（Montreal Cognitive Assessment, MoCA）、FAS量表及PASC症状评分进行评估。- 生物样本：采集血清与血浆样本用于蛋白质组学分析，采用Olink 3072 Explore平台结合邻近延伸测定（Proximity Extension Assay, PEA）技术，以及单分子阵列（Single Molecule Array, SIMOA）HD-X平台。- 影像学分析：在基线阶段开展脑部磁共振成像分析，包括皮层分区、顺磁磁化率检测、脉络丛分割以及沿血管周围间隙的弥散张量成像（diffusion tensor imaging along perivascular spaces, DTI-ALPS），以识别脑部结构改变。