Markers of limbic system damage following SARS-CoV-2 infection

Abstract

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate, or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms, and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (p = .03 corrected), as did severe patients for disgust (p = .04 corrected) and irritation (p < .01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or posttraumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort

“…First, our results confirmed that the neurocognitive consequences of SARS-CoV-2 infection go beyond any effect of ICU hospitalisation. More specifically, neuropsychological deficits at 6–9 and 12–15 months post-infection were found to be partially independent of the severity of the initial infection, thus supporting previous observations [ 1 , 6 , 9 , 10 , 43 – 45 ]. Moreover, concerning changes in the neuropsychological deficits, the results of our assessment at 12–15 months indicated a normalisation of attentional deficits in the moderate subgroup, the persistence of memory and logical reasoning symptoms in both the moderate and severe subgroups, and deteriorations in both instrumental functioning and executive functions in the moderate and severe subgroups.…”

Tracts in the limbic system show microstructural alterations post COVID-19 recovery

“…decrease in episodic memory, objective cognitive decline, weakened attention and fatigue. 21-23 This hypothesis is strengthened by neuroimaging studies that report significant loss in limbic functional connectivity and grey matter volume. 15 , 18-20 , 28 , 50-53 Microstructural alterations in the tracts involved in the limbic system, as observed in our study, could be a precursor to these functional deficits.…”

“… 54 Moreover, microstructural damage in the limbic white matter could be a precursor to the widely reported functional deficits like decline in episodic memory, attention and cognitive abilities. 21-23 In some tracts, the observed increased myelination and axonal growth may represent the result of a compensatory or recovery mechanism in response to COVID-related damage to other tracts. Moreover, the observations of this study are also consistent with neurological case studies on COVID-19 patients and group-level studies conducted using DWI and other MRI modalities.…”

“… 19 Another comprehensive multi-modal MRI study reported that cognitive dysfunction in COVID survivors showed significant association with neuroimaging biomarkers like grey matter volume and functional connectivity in limbic areas. 20 Neuropsychiatric and cognitive tests have repeatedly reported a decline in episodic memory, attention and mild cognitive deficits in COVID survivors, 21-23 suggesting the involvement of the limbic system in these impairments. These studies provide a refined view of the neurological impacts of COVID-19 for future investigations.…”

Transcutaneous vagus nerve stimulation improves Long COVID symptoms in a female cohort: a pilot study

“…Cognitive impairment (e.g., attention or memory issues), commonly reported as “brain fog,” is highly prevalent in Long COVID, affecting approximately 80% of long haulers ( 11 ). Neuroimaging studies have detected damages in various limbic and associative brain regions following COVID-19 infection, likely indicative of neuroinflammation and possible neurodegeneration ( 12 , 13 ). Notably, chronic loss of smell correlates with cognitive decline and is an early predictor of Alzheimer’s disease ( 14 ).…”