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. 2022 Oct 26:awac384. doi: 10.1093/brain/awac384

Multimodal neuroimaging in post-COVID syndrome and correlation with cognition

María Díez-Cirarda 1,, Miguel Yus 2, Natividad Gómez-Ruiz 3, Carmen Polidura 4, Lidia Gil-Martínez 5, Cristina Delgado-Alonso 6, Manuela Jorquera 7, Ulises Gómez-Pinedo 8, Jorge Matias-Guiu 9, Juan Arrazola 10, Jordi A Matias-Guiu 11,
PMCID: PMC9620345  PMID: 36288544

Abstract

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction.

Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected.

Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found.

The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

Keywords: post-COVID syndrome, cognitive impairment, functional connectivity, grey matter, white matter


Diez-Cirarda et al. report persistent structural and functional brain alterations, in cortical and subcortical structures, 11 months after acute SARS-CoV-2 infection. The changes were associated with cognitive dysfunction, and suggest several pathophysiological mechanisms relevant to post-COVID syndrome.

Contributor Information

María Díez-Cirarda, Department of Neurology. Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Miguel Yus, Department of Radiology, Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Natividad Gómez-Ruiz, Department of Radiology, Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Carmen Polidura, Department of Radiology, Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Lidia Gil-Martínez, Department of Radiology, Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Cristina Delgado-Alonso, Department of Neurology. Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Manuela Jorquera, Department of Radiology, Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Ulises Gómez-Pinedo, Department of Neurology. Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Jorge Matias-Guiu, Department of Neurology. Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Juan Arrazola, Department of Radiology, Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Jordi A Matias-Guiu, Department of Neurology. Hospital Clínico San Carlos. Health Research Institute “San Carlos” (IdISCC). Universidad Complutense de Madrid. Madrid, Spain.

Supplementary Material

awac384_Supplementary_Data

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Supplementary Materials

awac384_Supplementary_Data

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