ABSTRACT
Background: Little is known about the underpinning mechanisms of neurological dysfunction in post-COVID syndrome. Methods: We conducted a cross-sectional study of 87 consecutive subjects after a mild infection, with a median of 54 days after diagnosis of COVID-19. We performed structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. The MRI study included white matter investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). Results: Subjects self-reported headaches (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68% of participants), excessive somnolence (35%), symptoms of anxiety (29%), impaired cognitive flexibility (40%), and language dysfunction (33%). Besides, we observed a correlation between DTI fractional anisotropy (FA) and abnormal attention and cognitive flexibility in the Trail Making Test part B. Elevated levels of fatigue and somnolence associated with higher connectivity of the posterior cingulate cortex (PCC) in the RS-fMRI study of the default mode network. While higher connectivity of the PCC with bilateral angular gyri was associated with higher fatigue levels, the elevated levels of somnolence correlated with higher connectivity between the PCC and both the left thalamus and putamen. Conclusions: COVID-19 is associated with long-term neuropsychiatric symptoms and cerebral functional and microstructural alterations.
Subject(s)
Anxiety Disorders , Language Disorders , Fatigue , Headache , Disorders of Excessive Somnolence , Attention Deficit Disorder with Hyperactivity , Nervous System Diseases , Mobility Limitation , COVID-19 , Brain Diseases , Cognition DisordersABSTRACT
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 [fi]ber 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 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 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.
Subject(s)
Coronavirus Infections , Scotoma , Ossification of Posterior Longitudinal Ligament , Leukoencephalopathies , COVID-19 , FatigueABSTRACT
Although post-acute cognitive dysfunction and neuroimaging abnormalities have been reported after hospital discharge in patients recovered from COVID-19, little is known about persistent, long-term alterations in people without hospitalization. We conducted a cross-sectional study of 87 non-hospitalized recovered individuals 54 days after the laboratory confirmation of COVID-19. We performed structured interviews, neurological examination, 3T-MRI scans with diffusion tensor images (DTI) and functional resting-state images (fMRI). Also, we investigated fatigue, anxiety, depression, somnolence, language, memory, and cognitive flexibility, using validated instruments. Individuals self-reported a high frequency of headache (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68%), excessive somnolence (35%), anxiety (29%), impaired cognitive flexibility (40%) and language impairment (33%). There were widespread cerebral white matter alterations (mainly characterized by increased fractional anisotropy), which correlated with abnormal attention and cognitive flexibility. The resting-state fMRI networks analysis showed severely disrupted brain hyperconnectivity and loss of resting-state networks specificity.
Subject(s)
Anxiety Disorders , Language Disorders , Fatigue , Headache , Disorders of Excessive Somnolence , Depressive Disorder , Mobility Limitation , COVID-19 , Brain Diseases , Cognition DisordersABSTRACT
COVID-19 patients may exhibit neuropsychiatric and neurological symptoms. We found that anxiety and cognitive impairment are manifested by 28-56% of SARS-CoV-2-infected individuals with mild respiratory symptoms and are associated with altered cerebral cortical thickness. Using an independent cohort, we found histopathological signs of brain damage in 25% of individuals who died of COVID-19. All of the affected brain tissues exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Infection of neural stem cell-derived astrocytes changed energy metabolism, altered key proteins and metabolites used to fuel neurons and for biogenesis of neurotransmitters, and elicited a secretory phenotype that reduces neuronal viability. Our data support the model where SARS-CoV-2 reaches the brain, infects astrocytes and triggers neuropathological changes that contribute to the structural and functional alterations in the brain of COVID-19 patients.
Subject(s)
Anxiety Disorders , Signs and Symptoms, Respiratory , Brain Injury, Chronic , Astrocytoma , Severe Acute Respiratory Syndrome , Mental Disorders , COVID-19 , Cognition DisordersABSTRACT
COVID-19 patients may exhibit neuropsychiatric and/or neurological symptoms. We found that anxiety and cognitive impairment are manifested by 28-56% of SARS-CoV-2-infected individuals with mild or no respiratory symptoms and are associated with altered cerebral cortical thickness. Using an independent cohort, we found histopathological signs of brain damage in 19% of individuals who died of COVID-19. All of the affected brain tissues exhibited foci of SARS-CoV-2 infection, particularly in astrocytes. Infection of neural stem cell-derived astrocytes changed energy metabolism, altered key proteins and metabolites used to fuel neurons and for biogenesis of neurotransmitters, and elicited a secretory phenotype that reduces neuronal viability. Our data support the model where SARS-CoV-2 reaches the brain, infects astrocytes and triggers neuropathological changes that contribute to the structural and functional alterations in the brain of COVID-19 patients.