Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19

Abstract

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.

Long COVID‐19: Objectifying most self‐reported neurological symptoms

“…Although visual inspection of structural MRI excluded macrostructural abnormalities, deeper examination of functional connectivity, structural changes, and brain metabolism may reveal the neural correlates underlying frequently reported neurological complaints. First quantitative MRI imaging studies provide evidence of altered brain integrity 15 , 45 and alterations in orbitofrontal and temporal brain regions 14 possibly underlying these abnormalities during the post‐acute phase. The discrepancy between self‐reported symptoms and objective measurements should hence not diminish the importance of Long COVID‐19 , but further fuel our research efforts to understand its neurobiology.…”

“…13 However, very early preprint studies indicate subtle structural and functional changes detected by specialized quantitative imaging analyses in non-hospitalized patients as well. 14,15 To sum up, qualitative studies covering the different aspects of the Long COVID-19 spectrum contextualizing imaging, neuropsychological and clinical findings in a clinical feasible setting are urgently needed to help physicians and patients properly manage the disease.…”

“… 13 However, very early preprint studies indicate subtle structural and functional changes detected by specialized quantitative imaging analyses in non‐hospitalized patients as well. 14 , 15 …”

The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline

“…White matter changes, in general, were characterized by lower diffusivity and higher fractional anisotropy (with no differences in total white matter volume), indicating a potential remyelination [121]. Additionally, resting-state fMRI findings in individuals recovered from mild COVID-19 showed states of hyperconnectivity [122]. These neuroimaging findings demonstrate that structural brain changes are possible, even spanning across non-severe cases, but regardless, more imaging studies are necessary, including in recovered COVID-19 patients, to better quantify risk and potential long-term consequences.…”

Broken Connections: The Evidence for Neuroglial Failure in ME/CFS

“…Of further note, the LC may work in resonance with the salience network (SN), an area including the anterior cingulate cortex that has been implicated in ME/CFS 5,376 (and now also in Long Covid). 377,378 So it may be no surprise that the LC, with its far reaching, multi-level involvement in stress and arousal regulation, has been implied in ME/CFS (and other diseases like posttraumatic stress disorder). 379 Physiologically, both the stress response and the immune response seem to be intricately linked because the stress response is based on intense crosstalk with the transcription factor Nuclear Factor-kappa B (NF-κB), a potent activator of the innate immune response and implied by several groups in the pathology of ME/CFS 380,381 and indeed closely related to fatigue symptomatology.…”