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Advanced Neurology SARS-CoV-2 in age-associated neurodegeneration

prognostic tools for evaluating the risk of developing immunosenescent phenotypes would be highly beneficial
specific age-related neurological diseases. One promising for developing new therapeutics and targets. Past studies
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strategy involves repurposing existing drugs, which are reported the presence of Aβ42 and Aβ40, described
not only cost-effective but also may partially mitigate long- as abnormal neuro-PASC in the CSF, which indicates
term impact. 17,125 Drugs such as remdesivir (a polymerase impaired amyloid processing in long-term COVID
inhibitor initially developed for hepatitis C virus) and patients. 87,133 Peripheral biomarkers for CNS injury, such
molnupiravir (originally developed for Venezuelan equine as plasma neurofilament light chain and plasma glial
encephalitis and influenza) have efficiently reduced fibrillary acidic protein, could serve as prognostic markers
hospitalization and death, but their long-term efficacy for long-term COVID-associated CNS impairment.
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is yet to be evaluated. Other drugs targeting SARS- Other emerging approaches to mitigate the risk of long-
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CoV-2 proteins, such as polymerase, helicase, replication- term COVID-associated neurological diseases include
transcription complex, proofreading mechanisms, and antioxidant therapy, probiotics, and small-molecule
5’-capping, are under investigation. 125,127 Developing inhibitors. For instance, antioxidants such as resveratrol,
pharmacological agents targeting these pathways could ascorbic acid, Q10, fisetin, and quercetin have been
be beneficial in preventing viral persistence in brain cells, shown to improve the redox environment post-COVID.
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although clinical trials should focus on the efficacy of such Available treatments with antioxidants and probiotics
drugs in crossing the BBB. may help restore intestinal flora, potentially reducing
An innovative approach involves a soluble recombinant the peripheral inflammatory response and ameliorating
form of the ACE2 receptor, which prevents the viral spike chronic neuroinflammation (Table 4).
protein from binding to cell surfaces and reduces viral The SARS-CoV-2 pandemic has exposed significant
load in vivo. Inflammatory mediators, including IL-1, gaps in our understanding of viral persistence and its effects
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IL-2, 1L-6, 1L-7, 1L-1β, granulocyte-macrophage colony- on brain aging. While traditional research on neuro-aging
stimulating factor, and IFNs, play critical roles in chronic focused on neurotropic viruses, the concept of “neuro-
neuroinflammation, encephalitis, and increased risk of COVID” has emerged, illustrating how COVID-19 can
age-related disease. IL-6 concentrations, in particular, impair neurological function and cognitive abilities. By
correlate with viral load and are elevated in acute cases. combining recent advancements with existing knowledge,
Early studies with tocilizumab, which binds to IL-6 researchers have the potential to improve the diagnosis,
receptors, showed mixed results, suggesting IL-6 could be a treatment, and management of COVID-19-associated
prognostic marker for long-term neurological sequelae. neurodegeneration, ultimately enhancing the quality of life
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Future clinical trials should encompass patients with for affected individuals.
acute COVID-19, mild COVID-19, and long COVID-19
to compare cytokine profiles and cognitive symptoms. 8. Discussion and future directions
This approach could help identify novel tissue-specific The severe outcomes of SARS-CoV-2 infection are likely
biomarkers that could mitigate the long-term impact of driven by a pathological hyperinflammatory response,
SARS-CoV-2 on the CNS. initiating unregulated local tissue damage, systemic
Janus kinase inhibitors target key pro-inflammatory cytokine storm, vascular leakage, and thrombosis. These
cytokines and provide transient protection against events contribute to both immediate symptoms and
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excessive cytokine release. Clinical trials targeting other neurological deficits. 1,2,135,136 As described earlier, viral
inflammatory mediators are underway; however, the most invasion of the brain can occur through multiple routes.
commonly used monoclonal antibody against TNF – a Viral persistence in the brain is speculated to be caused
valuable marker of brain aging – has not yet been decisively by (i) early defects in the IFN-1 response, which fails to
evaluated for long COVID patients. Special attention clear the pathogen or its remnants from the primary site
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should be given to understanding the complex interaction of infection and blood; (ii) failure of the host immune
between the immune system and the coagulation pathway, system to recognize the processed viral genome; and
which could lead to microclot formation in brain blood (iii) dysregulated immune cell infiltration into the brain.
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vessels, increasing the risk of ischemic stroke and other Despite these insights, the exact molecular mechanisms
neurological complications. 132 associated with progressive neuronal loss remain unclear,
Previous research into biomarkers suggests that levels of necessitating direct experimental evidence to evaluate the
extracellular vesicles, immune markers, and oligopeptides role of viral proteins in neurodegeneration.
may be indicative of long-term COVID-associated Studies on long-term COVID suggest the potential
neurodegeneration. 17,66 Discovering biomarkers that indicate involvement of neurological autoimmune diseases,

Volume 3 Issue 4 (2024) 16 doi: 10.36922/an.4267