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Advanced Neurology SARS-CoV-2 mechanisms of neurological impact

NLRP3 inflammasome activation, and Aβ production in the renin-angiotensin system, have been observed
underscores the need for further research to elucidate the in COVID-19 patients. SARS-CoV-2 binds to ACE2,
mechanisms by which viral infections may contribute to reducing its availability and leading to an increased ACE/
neurodegenerative diseases. ACE2 ratio. This imbalance heightened inflammatory
responses, promoted the production of ACE-dependent
7.3. The intersection of AD and COVID-19: ACE2 as a cytokines, induced oxidative stress, and diminished the
mediator of viral entry and neurodegeneration protective effects typically mediated by ACE2. 171,186-188
In AD patients, there is an observed increase in the As a result, elevated ACE2 expression, particularly
expression of ACE2, which serves as the cellular receptor in the context of neurodegenerative diseases like AD,
for SARS-CoV-2, facilitating viral entry into host may represent a significant risk factor for increased
cells. ACE2 is notably expressed in neurons and glial susceptibility to SARS-CoV-2 infection. The intersection
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cells, with higher concentrations in the temporal lobe of these factors emphasizes the need for further research
and hippocampus – regions critically involved in AD into the role of ACE2 in both the pathophysiology of
pathology. Although ACE2 expression does not exhibit neurodegenerative diseases and the mechanisms of viral
significant age-dependent variation, evidence suggests infection.
a correlation between elevated ACE2 levels and the
development or progression of AD. In the context of 8. Potential therapeutic approaches for
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COVID-19, ACE2 plays a crucial role by mediating the neurological complications of COVID-19
entry of SARS-CoV-2 into cells, contributing to the virus’s
pathogenic effects. Beyond its role in neuronal and glial At present, no proven therapeutic regimen specifically
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cells, ACE2 is expressed in epithelial and endothelial cells, targets the neurological complications associated with
which is essential for understanding the mechanisms by COVID-19, despite growing recognition of these issues.
which SARS-CoV-2 infiltrates the body and exacerbates However, various potential therapies are being explored to
disease progression. The increased ACE2 expression address conditions such as CI, stroke, encephalopathy, and
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in AD-affected brain regions may not only facilitate Guillain–Barré syndrome (GBS) that may arise following
viral entry but also contribute to the neurodegenerative SARS-CoV-2 infection. Promising therapeutic strategies
effects observed in COVID-19, highlighting a potential are under investigation, with the potential to mitigate the
intersection between viral infection and neurodegenerative neurological impact of COVID-19.
disease pathways (Table 4). 176-178
8.1. CI and AD drugs
In the nervous system, ACE2 expression is generally
low compared to other tissues. However, SARS-CoV-2 CI associated with COVID-19, particularly in long-haul
may still infiltrate the brain through the olfactory nerve, cases, is a significant concern, as affected individuals often
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particularly in individuals with compromised BBB integrity experience persistent brain fog or memory problems. Some
– a common feature of neurodegenerative disorders such researchers are exploring the repurposing of AD drugs, such
as AD. 132,179-182 This potential route of entry underscores the as aminoadamantane and memantine, as potential treatments
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vulnerability of the CNS to viral invasion in the presence of for cognitive deficits caused by the virus (Table 5). These
pre-existing neurological damage. drugs, which act on glutamatergic pathways, might improve
cognitive function by reducing excitotoxicity, a mechanism
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Immunofluorescence staining and single-cell gene atlas implicated in both AD and COVID-19-induced brain
studies revealed that ACE2 is predominantly expressed damage. While these options are still speculative, they
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in type II alveolar epithelial cells and airway epithelial represent a key area of future research.
cells. These findings provide critical insights into the
mechanisms of viral infection and highlight the role of 8.2. Revascularization and erythrocyte metabolism
ACE2 in facilitating SARS-CoV-2 entry into host cells. restoration
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Furthermore, the presence of ACE2 in saliva has been Another promising approach to addressing COVID-19-
suggested as a potential diagnostic marker for COVID-19, related neurological complications involves improving
reflecting its widespread expression and involvement in cerebral blood flow and oxygen delivery to damaged
viral entry. 184 brain tissue. Hyperbaric oxygen therapy (HBOT) is
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In patients with comorbid conditions such as diabetes one technique under investigation, which delivers 100%
and hypertension, there is often an imbalance between ACE oxygen under pressure to stimulate brain recovery. HBOT
and ACE2, which exacerbates endothelial dysfunction. has demonstrated potential in improving revascularization
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Elevated plasma levels of angiotensin II, a key mediator and restoring erythrocyte metabolism, both of which

Volume 4 Issue 2 (2025) 23 doi: 10.36922/an.4909