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Advanced Neurology SARS-CoV-2 mechanisms of neurological impact

Table 1. Key aspects, critical findings, implications, and knowledge gaps in the current understanding of post‑acute sequelae of
SARS‑CoV‑2 infection
Aspect Key findings References
Definition of PASC PASC refers to the persistence or emergence of new symptoms following the acute phase of COVID-19. 28
These symptoms can affect individuals across a broad spectrum of initial illness severity, ranging from
mild to critical cases.
Prevalence of symptoms • A vast majority of patients, both hospitalized and non‑hospitalized, continue to experience symptoms 29
3 months after COVID-19 infection.
• The most commonly reported symptoms include fatigue and dyspnea, with only approximately 1% of
individuals reporting complete resolution of symptoms.
Neurological sequelae • Both acute and chronic neurological symptoms have been documented, including anxiety, sleep 30-36
disturbances, myalgia, and memory impairments.
• Rare but severe neurological syndromes, such as seizures, vasculitis, encephalopathy, and acute
inflammatory demyelinating polyneuropathy, have also been reported.
Focus of existing research • Existing research predominantly focuses on the neurological outcomes of severe COVID‑19 cases. 32-34
• There is a notable paucity of studies examining long‑term neurological outcomes in individuals who
experienced mild or moderate infections.
Risk factors for PASC • The risk factors for developing PASC are not yet fully understood, necessitating further research. 37-39
• Severe acute illness is associated with a higher likelihood of developing PASC; however, emerging
evidence suggests that individuals with mild or moderate COVID-19 may also face a substantial risk.
• The role of pre‑existing neurological conditions in the development of PASC remains underexplored,
representing a critical research gap.
Impact on quality of life • Neurological symptoms, particularly fatigue and headache, have significantly impacted the quality of life 31,40,41
in approximately 80% of COVID-19 survivors.
• An Italian self‑reported survey indicated that around 75% of participants experienced persistent fatigue,
muscle pain, and joint pain 3 months post‑infection.
• At 6 months, cognitive impairments, such as memory deficits and difficulty concentrating, became more
prominent.
Mortality and long COVID • The risk of mortality associated with long COVID appears to correlate strongly with the severity of the 42
severity acute COVID-19 infection.
• Notably, even patients who experienced mild illness during the acute phase have been found to have
persistent symptoms, with one-third of mild cases reporting fatigue, dyspnea, cognitive disturbances,
and anosmia up to a year post-infection.
Diagnostic criteria • While formal diagnostic criteria for PASC remain undefined, it is generally accepted that symptoms 43-46
persisting for 4 – 12 weeks after infection can be classified as PASC.
• Follow‑up studies indicated that between 25% and 75% of patients report symptoms extending up to
6 months, even among those who had mild cases.
Neurological and • Common neurological and psychiatric symptoms associated with PASC include persistent headaches, 47-53
psychiatric symptoms anosmia (loss of smell), sleep disturbances, fatigue, and cognitive dysfunction, such as difficulties with
concentration, language, and executive function.
• Depression and anxiety have been frequently reported among PASC patients.
• Autonomic dysfunction, including orthostatic intolerance, has also been observed in some individuals.
Research needs • There is an urgent need for the development of more robust diagnostic criteria for PASC, along with a 54,55
deeper understanding of its risk factors and effective treatments.
• Comprehensive longitudinal studies are crucial to unravel the long‑term neurological and psychiatric
impact of COVID-19, particularly in relation to neurodegeneration and cognitive decline.
Abbreviations: COVID‑19: Coronavirus disease 2019; PASC: Post‑acute sequelae of SARS‑CoV‑2 infection.

exhibited symptoms 3 months post-infection, with severe cases, fewer studies have explored the long-term
fatigue and dyspnea being the most prevalent, while only neurological outcomes in patients with mild infections. 32-34
approximately 1% of individuals reported being symptom- Case reports have described rare neurological syndromes,
free. Similar findings have been reported in other studies including seizures, vasculitis, encephalopathy, and acute
29
documenting both acute and chronic neurological sequelae, inflammatory demyelinating polyneuropathy (Table 1). 35,36
such as anxiety, sleep disturbances, myalgia, and memory However, larger cohort studies are lacking, highlighting
impairments. 30,31 Although most research has focused on the need for comprehensive longitudinal research.

Volume 4 Issue 2 (2025) 14 doi: 10.36922/an.4909