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

dysfunction, and hypoxia contribute to neurological 9. Conclusion
deficits, opening new avenues for combating these
symptoms. 95,102,107 Oxidative stress and mitochondrial In conclusion, the neurological aftermath of SARS-CoV-2
dysfunction are critical factors in neurodegenerative infection is a multifaceted issue requiring comprehensive
diseases, and their association with long-term COVID research and clinical strategies. Studies suggest that up
suggests that targeting these pathways could alleviate to 30-50% of individuals who recover from COVID-
neurological symptoms. In addition, hypoxia, resulting 19 report persistent neurological symptoms, including
from impaired respiratory function, exacerbates neuronal cognitive impairment, fatigue, and headache. The risk
damage and contributes to cognitive deficits. Addressing and severity of neuro-COVID are notably higher in
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these factors through targeted therapies could alleviate the older adults, partly due to age-related brain changes
neurological burden of long-term COVID-19. and immune dysregulation. For instance, in individuals
aged 65 and above, the risk of developing dementia-like
In the future, fundamental research will drive the symptoms post-COVID is roughly doubled compared to
development of therapies that can be tested in larger those without a COVID history. Imaging studies indicate
clinical trials. Therapies that have shown promise in that SARS-CoV-2 can lead to structural changes, such as a
treating HIV- and H1N1-related cognitive impairment reduction in gray matter in the frontal and temporal lobes,
should be evaluated for their effectiveness against neuro- which are linked to cognitive functions. One study found
COVID. One potential strategy involves resetting that, even in mild cases, patients exhibited brain volume
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microglia to their homeostatic, non-reactive states, which loss comparable to that typically seen in a decade of natural
could benefit a wide range of neurological disorders. In aging. Beyond physical neurological symptoms, COVID-
addition, enhancing neural plasticity mechanisms, even 19 survivors have an increased prevalence of mental health
in the presence of ongoing neuroinflammation, could issues, including anxiety, depression, and PTSD. In a study,
help alleviate cognitive symptoms. Another critical area of over 30% of long COVID patients experienced moderate
research is determining whether inflammation is driven to severe depression symptoms, underscoring the need
by persistent viral infection or viral remnants in the for integrated mental health support. By understanding
lungs, intestinal tract, and other reservoirs. Identifying the underlying mechanisms and developing targeted
the root cause of distal inflammation could help reduce therapies, we can mitigate the long-term impact of
the neurological burden of long-term COVID-19 by COVID-19 on brain health and improve the quality of
eliminating the primary source of inflammation. This life for survivors. Effective management of long-term
approach necessitates comprehensive studies on viral COVID-associated neurodegeneration hinges on a holistic
persistence and the long-term effects of SARS-CoV-2 approach that addresses the intricate relationship between
infection on various organs. viral persistence, immune response, and brain aging.
Effective clinical management of long-term COVID-
associated neurodegeneration requires a multidisciplinary Acknowledgments
approach that includes comprehensive assessment and We would like to acknowledge the Department of
monitoring, targeted therapies, symptomatic management, Biotechnology, Ministry of Science and Technology,
and preventive measures. Such an approach involves Government of India, and the Indian Institute of Chemical
collaboration between neurologists, immunologists, Biology, Kolkata, India. All the figures were created in
psychiatrists, and primary care physicians to address the BioRender.
complex interplay of viral persistence, immune response,
and brain aging. Regular monitoring of patients for Funding
18
neurological symptoms and cognitive decline is essential This work was supported by the Department of
for early intervention and management. Targeted therapies Biotechnology (DBT) (DBT-RA/2023-24/Call-I/RA/07
should focus on reducing neuroinflammation, oxidative and BT/PR51484/MED/122/359/2024), India, and Indian
stress, and mitochondrial dysfunction while enhancing Institute of Chemical Biology, Kolkata, India.
neural plasticity and cognitive function. 17,87,139 Symptomatic
management should address specific symptoms, such Conflict of interest
as cognitive impairment, depression, and anxiety,
through both pharmacological and non-pharmacological The authors declare that they have no competing interests.
interventions. Preventive measures, including vaccinating, Author contributions
promoting overall health, and implementing strategies to
reduce the risk of severe COVID-19 infection, are also Conceptualization: Sourish Ghosh
essential. Writing - original draft: Ankita Sarkar

Volume 3 Issue 4 (2024) 18 doi: 10.36922/an.4267