Page 21 - AN-4-2

Advanced Neurology SARS-CoV-2 mechanisms of neurological impact

2.2. Risk factors and pre-existing conditions criteria, risk factors, and effective treatments. The growing

The risk factors for developing PASC remain poorly body of evidence highlights the need for comprehensive,
understood and require further investigation to achieve a longitudinal studies to address the long-term consequences
54,55
more thorough understanding. While severe acute illness of COVID-19 on the nervous system.
has been associated with a higher risk of developing 3. Persistence, the emergence of new
PASC, emerging evidence suggests that individuals with
37
mild or moderate COVID-19 may also be at considerable disorders, and long-term risks of neurological
risk. 38,39 Moreover, there is a lack of comprehensive data impact associated with SARS-CoV-2
on the risk of developing PASC in individuals with pre- 3.1. Persistence of neurological disorders and the
existing neurological conditions, highlighting a critical gap emergence of new conditions
that warrants further investigation (Table 1).
Recent evidence has indicated that the severe acute phase
Many individuals who contracted COVID-19 of SARS-CoV-2 infection can both initiate the development
have reported a worsening of pre-existing symptoms. of and persist within the nervous system throughout both
Neurological symptoms, particularly fatigue and the acute and post-acute phases of infection. COVID-19
5,56
headache, have significantly affected the quality of life in has been linked to the emergence of new neurological
approximately 80% of patients. In line with these findings, disorders and the exacerbation of pre-existing conditions.
40
an Italian self-reported survey found that 3 months post- Individuals with pre-existing neurological conditions,
infection, about three-quarters of participants experienced such as dementia, Parkinson’s disease (PD), and epilepsy,
persistent fatigue, and around 60% reported muscle pain experience higher mortality rates when infected with
and joint pain. By 6 months post-infection, the dominant COVID-19. 57-59 Furthermore, the development of new
31
symptoms had shifted from fatigue and headache to neurological conditions in hospitalized COVID-19 patients
memory impairment and reduced concentration. has been associated with increased morbidity and mortality
40
Similarly, a cross-sectional online survey identified post- 60,61
exertional malaise, fatigue, and cognitive dysfunction as that extends beyond the acute phase of infection.
the most prevalent symptoms at the 6-month mark. 41 Studies on post-SARS-CoV-2 neurological sequelae,
often centered on hospitalized patients without appropriate
2.3. Long-term neurological and psychiatric controls, frequently report headaches and cognitive
symptoms dysfunction in both the acute and chronic phases. Less
The risk of mortality associated with long COVID appears common conditions include movement disorders,
to correlate with the severity of the acute infection. cerebrovascular disease, neuropathies, and seizures. 62,63
However, even individuals with mild COVID-19 are at Large-scale studies comparing COVID-19 with other viral
risk of developing PASC. A year-long study reported illnesses or SARS-CoV-2-negative controls have shown
that one-third of patients with mild illness experienced an increased risk of neurological complications, though
persistent symptoms, including fatigue, dyspnea, cognitive these studies often suffer from issues related to timing and
disturbances, and anosmia. Although formal diagnostic geographical mismatch (Table 2). 6,14,17
42
criteria for PASC have yet to be established, it is generally There has been increasing attention on PASC,
defined as symptoms persisting for 4 – 12 weeks following characterized by symptoms that persist beyond 3 months
infection. Follow-up studies have demonstrated that after the initial infection. Neurological manifestations
43
between a quarter and three-quarters of patients report of PASC include neurocognitive deficits, autonomic
symptoms lasting up to 6 months, even in cases of mild dysfunction, pain, mood disorders, and anosmia. 64-67 Recent
illness. 44-46
studies have observed a higher risk of encephalopathy,
The neurological and psychiatric symptoms stroke, movement disorders, neuropathy, neurocognitive
associated with PASC include headaches, anosmia, dysfunction, anxiety, fatigue, seizures, and headaches in
48
47
sleep disturbances, and CIs, such as difficulties with the post-acute phase compared to SARS-CoV-2-negative
49
concentration, language, and executive function. Other or historical controls. 17,68-70 However, replication of these
50
commonly reported symptoms include depression and findings has been inconsistent. 71,72
anxiety. In addition, autonomic dysfunction, such as
51
orthostatic intolerance, has been reported (Table 1). 52,53 3.2. Long-term risks and challenges in studying
post-COVID neurological impact
While much remains to be understood about PASC,
its neurological and psychiatric impacts are clear, and Studies have identified elevated risks for various
warrant continued research to better define diagnostic neurological conditions following SARS-CoV-2 infection,

Volume 4 Issue 2 (2025) 15 doi: 10.36922/an.4909