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Advanced Neurology SARS-CoV-2 mechanisms of neurological impact

controls. Although COVID-19 prevalence was higher to mitigate neuro-PASC and related neurodegenerative
among PD patients, mortality rates were comparable conditions. Collaborative studies exploring immune
to those of non-PD patients. Comorbidities such as responses, genetic factors, and neuroinflammatory
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hypertension and diabetes may complicate the severity of pathways will be crucial in advancing our understanding
COVID-19 in PD patients. While direct evidence linking of how COVID-19 influences both short- and long-term
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SARS-CoV-2 to PD is lacking, ACE2 receptors, which are neurological outcomes.
widely expressed in the CNS, including regions related to
PD, may play a role in susceptibility. The SARS-CoV-2 5. BBB disruption as a key driver of CI in
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E protein may activate Toll-like receptor 2 in microglia, COVID-19 and long COVID
potentially influencing both AD and PD. 112 Recent research highlights the critical importance of
COVID-19 may exacerbate pre-existing conditions BBB integrity in the neurological effects of SARS-CoV-2
or trigger subclinical neurodegenerative diseases. For infection. 25,116 The BBB, primarily composed of endothelial
instance, individuals with AD were particularly vulnerable cells lining the cerebral vasculature, acts as a selective
to SARS-CoV-2, experiencing a higher mortality risk. barrier that regulates molecular exchange between the
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This increased susceptibility may be attributed to pre- bloodstream and the brain (Table 3). This protective
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existing neuroinflammation and the inflammatory function is maintained by the coordinated efforts of
response triggered by COVID-19. Biomarkers associated astrocytes, pericytes, microglia, neurons, and the basement
with AD, such as serum total tau and neurofilament light membrane, which together ensure barrier integrity
chain, were positively correlated with infection severity, through mechanisms such as tight junctions, transporters,
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suggesting poorer outcomes among hospitalized COVID- and efflux systems. 118
19 patients. Neuroinflammation driven by SARS-CoV-2 Postmortem examinations of tissues from COVID-
may contribute to degenerative lesions and an increased 19 patients have revealed significant microvascular
risk of AD (Table 3). 114 damage, including fibrinogen leakage and thinning
Electroencephalogram (EEG) abnormalities may of the endothelial basal lamina, particularly in the
provide valuable insights into neurological complications olfactory bulb. Spatial transcriptomic studies further
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and cognitive decline in long COVID patients. indicated alterations in the vascular and immune systems,
Understanding the overlapping pathophysiological characterized by serum protein leakage and platelet
mechanisms, such as neuroinflammation and astrocyte accumulation. These findings, along with similar
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reactivity, can deepen our understanding of AD and the observations in animal models, suggest that SARS-CoV-2
effects of COVID-19 on cognitive function (Table 3). or its spike protein may compromise the BBB. However,
Insights from neurophysiology and AD and related the precise cerebrovascular pathology, particularly in long
dementias (ADRD) research could inform how reactive COVID, remains incompletely understood.
astrocytes contribute to neurovascular comorbidities Unlike other zoonotic coronaviruses, such as severe
observed in COVID-19, highlighting research gaps related acute respiratory syndrome and Middle East respiratory
to cognitive EEG findings and mild CI in long COVID. 115 syndrome, which rarely cause neurological complications,
Some individuals recovering from COVID-19 exhibit SARS-CoV-2 appears to induce more frequent BBB
CIs similar to those seen in neurodegenerative diseases, disruption, particularly in patients with CIs like brain
particularly ADRD. Evidence suggests that COVID-19 fog. This association suggests that BBB integrity may
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and ADRD share common impacts on synaptic and serve as a potential biomarker for neurological damage in
neurovascular dysfunctions, involving astrocyte reactivity COVID-19, with therapies aimed at preserving or restoring
and neuroinflammation. Cognitive symptoms associated the BBB offering a promising approach for managing long
with COVID-19 may be driven by neurophysiological COVID-related symptoms. 121
abnormalities akin to those observed in ADRD, which may Systemic inflammation during SARS-CoV-2 infection
be detectable through routine EEG exams. 115 is a major driver of BBB dysfunction. Elevated levels of
Given the shared pathophysiological mechanisms serum proteins, including S100 calcium-binding protein
between COVID-19 and neurodegenerative diseases, B (S100β), IL-6, basic fibroblast growth factor, and IL-13,
including synaptic and neurovascular dysfunctions, further have been observed in actively infected patients. 122,123
research is essential to elucidate the long-term impact of S100β, a marker commonly associated with neurological
SARS-CoV-2 on cognitive health. Understanding these conditions such as epilepsy and traumatic brain injury, is
overlaps may help identify biomarkers for the early detection particularly elevated in COVID-19 patients experiencing
and guide the development of therapeutic interventions cognitive symptoms (Table 3). 122,123 In long COVID, BBB

Volume 4 Issue 2 (2025) 19 doi: 10.36922/an.4909