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

The clinical manifestations of severe acute respiratory affecting neurological health, particularly in the context of
syndrome coronavirus 2 (SARS-CoV-2) extend well age-associated neurodegenerative diseases. This condition,
beyond respiratory symptoms; a growing number of often referred to as long COVID or PASC, includes chronic
survivors report persistent and debilitating neurological fatigue, cognitive decline, and other neurological deficits
symptoms. This puzzling condition, now referred to as long that can accelerate age-related neurological symptoms. 16-18
COVID or neuro-COVID, is reshaping our understanding The definition of long COVID is often debated, especially
of brain health and disease. Neuro-COVID, or post-acute in the context of time frame (Figure 1). According to the
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consequences of COVID-19 (PASC), reveals a complex World Health Organization, post-COVID-19 disease
interplay between viral persistence, immune response, usually manifests 3 months after the onset of the infection,
and neurodegeneration, which significantly contributes with symptoms lasting at least 2 months and not attributed
to the aging process. Symptoms such as anosmia, senility, to another diagnosis. Similarly, the United Kingdom (UK)’s
cognitive impairment, depression, and anxiety reflect those National Institute for Health and Care Excellence describes
of aging, highlighting the profound impact of this disease. 6,7 long COVID as a multi-organ disease with debilitating
Recent advances suggest that neuroinflammation symptoms that emerge during the acute or mild phase of
alone can disrupt neuronal and glial cells, leading to the disease and persist for more than 4 weeks, with no
neurodegeneration and impaired neuropsychiatric alternative diagnosis. 19,20
and cognitive function. Beyond neuroinflammation, Statistics indicate that this debilitating illness affects at
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oxidative stress, deregulation of proteostasis, autoantibody least 10% of SARS-CoV-2 cases, with over 200 symptoms
production, and gut–brain dysregulation play critical roles impacting multiple organ systems. 17,20 Recent reports
in the development of neuro-COVID. 9-11 It is critical to estimate that at least 65 million individuals worldwide
recognize that these mechanisms, although not directly are suffering from long COVID, with cases steadily
related to SARS-CoV-2 infection, collectively alter the increasing. The incidence is estimated at 10 – 30% of non-
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architecture and function of distal tissues through the hospitalized cases, 50 – 70% of hospitalized cases, and 10 –
virus’s persistent presence in host tissues. The penetration of 12% of vaccinated cases. Numerous biomedical findings
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viruses across the blood–brain barrier (BBB) has increased have confirmed that long COVID can manifest in multiple
beyond the typical range of neurotropic viruses. 12,13 Over organ symptoms, including cardiovascular dysfunction,
the past few decades, the role of viral persistence in the thrombosis, cerebrovascular disease, and metabolic
development of neurodegenerative diseases has gained disorders. One potential cause of long COVID is the
significant global attention. The notorious SARS-CoV-2 persistent presence of SARS-CoV-2 in different tissues. 21,22
infection has underscored the urgency of investigating the
potential connection between viral persistence and the History data from previous pandemics and epidemics
onset and progression of age-associated neurodegenerative caused by RNA viruses in the last century provide ample
diseases such as Alzheimer’s disease (AD), Parkinson’s evidence of acute neurological effects. However, apart from
disease, and other forms of neurodegenerative diseases. 14,15 the 1918 H1N1 influenza pandemic and its associated
neurological consequences, there is little information
This comprehensive review aims to provide an overview on the long-term neurological consequences following
of the current understanding of the relationship between infection. Neurological and cognitive symptoms are
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SARS-CoV-2 infection and neurodegeneration. We focus prominent features of long COVID, including cognitive
primarily on the mechanisms by which the virus persists in impairment, sensorimotor symptoms, memory loss,
the brain, the viral proteins involved in these processes, and paresthesia, sensitivity to light and sound, dizziness,
the host pathways manipulated by the virus. In addition, balance issues, and autonomic dysfunction. A study
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we discuss recent therapeutic advances in this field and involving over 1.3 million people who had contracted
propose strategies for future improvements. Through COVID-19 reported that, while mental health issues
this investigation, we aim to shed light on paths toward such as anxiety and depression tended to resolve over
mitigating the long-term neurological effects of COVID-19 time, increased risks of cognitive impairment, seizures,
and improving brain health in the post-pandemic period. dementia, psychosis, and other neurocognitive conditions

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2. Deciphering the enigma of PASC in the persisted for at least 2-year post-infection. Interestingly,
context of neurodegenerative diseases patients with prior COVID-19 infection exhibit an average
decline in global cognitive performance equivalent to
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The SARS-CoV-2 pandemic, which began in 2019, has 10 years of aging. In addition, studies have detected
presented unforeseen challenges to global health, extending amyloid peptides, hallmarks of AD, in patients with long
beyond immediate respiratory impacts and significantly COVID. Collectively, the evidence suggests altered brain
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Volume 3 Issue 4 (2024) 2 doi: 10.36922/an.4267