Brain microstructural changes and fatigue after COVID-19

Diógenes Diego de Carvalho Bispo; Pedro Renato de Paula Brandão; Danilo Assis Pereira; Fernando Bisinoto Maluf; Bruna Arrais Dias; Hugo Rafael Paranhos; Felipe von Glehn; Augusto César Penalva de Oliveira; Neysa Aparecida Tinoco Regattieri; Lucas Scardua Silva; Clarissa Lin Yasuda; Alexandre Anderson de Sousa Munhoz Soares; Maxime Descoteaux

doi:10.3389/fneur.2022.1029302

Brain microstructural changes and fatigue after COVID-19

Front Neurol. 2022 Nov 10:13:1029302. doi: 10.3389/fneur.2022.1029302. eCollection 2022.

Authors

Diógenes Diego de Carvalho Bispo^{1

2

3}, Pedro Renato de Paula Brandão^{4

5}, Danilo Assis Pereira⁶, Fernando Bisinoto Maluf³, Bruna Arrais Dias³, Hugo Rafael Paranhos³, Felipe von Glehn^{2

5}, Augusto César Penalva de Oliveira⁷, Neysa Aparecida Tinoco Regattieri², Lucas Scardua Silva⁸, Clarissa Lin Yasuda⁸, Alexandre Anderson de Sousa Munhoz Soares², Maxime Descoteaux⁹

Affiliations

¹ Diagnostic Imaging Unit, Brasilia University Hospital, University of Brasilia, Brasília, Brazil.
² Faculty of Medicine, University of Brasilia, Brasília, Brazil.
³ Department of Radiology, Hospital Santa Marta, Taguatinga, Brazil.
⁴ Neuroscience and Behavior Laboratory, University of Brasilia, Brasília, Brazil.
⁵ Hospital Sírio-Libanês, Brasília, Brazil.
⁶ Advanced Psychometry Laboratory, Brazilian Institute of Neuropsychology and Cognitive Sciences, Brasília, Brazil.
⁷ Department of Neurology, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.
⁸ Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), University of Campinas, Campinas, Brazil.
⁹ Sherbrooke Connectivity Imaging Laboratory, University of Sherbrooke, Sherbrooke, QC, Canada.

Abstract

Background: Fatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods: We studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling.

Results: COVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 (±26.4) days. The COVID-19 group had higher total CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores, performance in reaction time, and visual memory tests correlated with microstructural changes in patients with COVID-19.

Conclusions: Quantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery.

Keywords: COVID-19; brain; cognition; diffusion magnetic resonance imaging; fatigue.