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Advanced Neurology SARS-CoV-2 mechanisms of neurological impact

a task-based fMRI study that showed altered connectivity 10. Conclusion and future directions
patterns in the right insula and right putamen, which were
linked to cognitive failure and may contribute to subjective The neurological impacts of SARS-CoV-2 span both the
cognitive decline. In addition, a 3-month follow-up study acute and post-acute phases, presenting a complex and
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reported decreased cortical thickness in the left putamen evolving landscape of symptoms and sequelae. The
of COVID-19 survivors, suggesting potential structural profound and multifaceted influence of SARS-CoV-2 on
neurological health ranges from the acute infection phase
damage. These findings might reflect compensatory to long-term outcomes. Persistent symptoms observed in
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brain mechanisms in response to damage, although the
exact cause of putamen impairment remains uncertain. PASC emphasize the need for ongoing surveillance and
research (Table 1). Initial studies have highlighted common
Various levels of damage to the temporal lobe, including manifestations such as fatigue, CI, and mood disorders.
the left superior temporal gyrus (STG) and right inferior However, substantial variability and uncertainty persist,
temporal gyrus (ITG), have been observed in COVID-19 particularly regarding mild infections and emerging
survivors. The temporal lobe plays a key role in emotional neurological disorders. 27
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regulation, sensory processing, memory, and language The complexity of neurological damage post-
comprehension. Damage to the STG has been linked to
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cognitive conditions such as subjective CI, mild CI, and COVID-19 is further compounded by systemic
dementia. 235,236 These findings align with structural MRI inflammation, immune dysregulation, and potential
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studies, which reported decreased cortical thickness in the autoimmune responses (Table 3). Although direct viral
STG of COVID-19 survivors 3 months after recovery. In invasion of the CNS is debated, evidence suggests that
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addition, increased ALFF values in the ITG were identified immune-mediated mechanisms and disruption of the BBB
in a 1-year follow-up resting-state fMRI study, suggesting play central roles in the neurological sequelae associated
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altered activity in this region post-COVID. 223,224,237,238 with long COVID. Genetic factors may also influence
susceptibility and severity, underscoring the need for
In addition, decreased spontaneous brain activity in personalized approaches in both managing and studying
the right superior parietal gyrus has been observed in these effects. 243
COVID-19 survivors. The superior parietal cortex is
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essential for visuospatial processing, attentional control, There is an urgent need for well-designed, long-term
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and working memory. A review on COVID-19-related cohort studies to monitor the progression of neurological
CI indicates that survivors may experience deficits in symptoms over time, especially in cases of mild and
memory, attention, and executive function, suggesting moderate COVID-19. Such studies should encompass
widespread brain damage. Supporting this, a recent diverse populations and account for pre-existing
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Mendelian randomization study found an association neurological conditions to provide a comprehensive
between severe COVID-19 and reduced cortical surface understanding of the spectrum of PASC. Comparative
area in the superior parietal gyrus, pericalcarine cortex, studies involving other viral infections and SARS-CoV-2-
and parahippocampal gyrus. These findings suggest that negative controls will help delineate specific neurological
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the superior parietal gyrus may be particularly vulnerable risks linked to COVID-19 and inform public health
to COVID-19-related damage, though the precise strategies.
mechanisms remain unclear (Table 6). Further research into the mechanisms underlying
Neuroimaging studies have identified significant brain neurological symptoms is essential, focusing on immune
abnormalities associated with COVID-19, particularly in dysregulation, systemic inflammation, and BBB integrity.
severe cases, where acute signal disruptions and lesions are Investigating how SARS-CoV-2 interacts with neural and
evident. Long-term structural changes, including reduced immune systems will clarify the pathways involved in
cortical thickness, alterations in white matter integrity, and neuro-PASC. Identifying reliable biomarkers for the early
diminished cerebral blood flow, have been prominently detection and monitoring of neurological complications is
observed in the frontal and limbic regions. To further also crucial. Biomarkers related to systemic inflammation
elucidate the impact of COVID-19 on brain health, future and neurodegenerative diseases could offer valuable
research should prioritize long-term neuroimaging follow- insights into the pathophysiology of PASC and aid in
ups, investigate the underlying mechanisms of brain damage, developing targeted interventions.
develop targeted therapeutic interventions, and explore The shared neuroinflammatory pathways between
potential recovery pathways. Comparative studies with other COVID-19 and AD provide a promising framework
viral infections may also provide critical insights into the for advancing our understanding of AD mechanisms,
unique neurobiological consequences of COVID-19. disease progression, and long-term cognitive decline

Volume 4 Issue 2 (2025) 27 doi: 10.36922/an.4909