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Advanced Neurology SARS-CoV-2 mechanisms of neurological impact

and, in extreme cases, death. However, ARDS associated transmembrane protease serine 2 (TMPRSS2) receptors,
1
with COVID-19 has also been found to trigger various with other potential entry pathways involving neuropilin
neurological manifestations, including encephalopathy, and vimentin, which are highly expressed in neurovascular
confusion, agitation, and corticospinal tract dysfunction. tissues. 18-20 Although the extent of viral neuroinvasiveness
Early in the pandemic, symptoms such as anosmia (loss remains debated, 21-23 recent evidence suggests that viral
of smell) and other neurological disturbances were RNA may persist in tissues, including the brain, long after
commonly reported. Since then, the phenomenon of the infection has resolved, much of which is derived from
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“long COVID,” or post-COVID syndrome, has emerged, postmortem studies. The mechanisms driving cognitive
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characterized by prolonged symptoms following the acute dysfunction in COVID-19 patients are still under
phase of infection. This condition manifests through a investigation. Preliminary findings suggest that SARS-
3,4
wide range of neurological, cognitive, and mental health CoV-2 may induce neuronal fusion, alter normal neuronal
symptoms. Among the most frequently reported is “brain activity, and lead to chronic neuroinflammation and
fog,” a non-specific term encompassing symptoms such premature brain aging, even in mild cases. 5,24,25 In addition,
as headaches, cognitive impairment (CI), and generalized gut dysbiosis and disruptions in serotonin pathways are
mental fatigue, all of which contribute to diminished believed to contribute to post-infection cognitive deficits. 26
concentration and executive functioning. Patients often
experience overwhelming fatigue, further exacerbating This article discusses the neurological impact of
cognitive difficulties, and commonly report mood COVID-19, with a particular focus on long COVID and
disturbances, including anxiety and depression. Sleep its cognitive consequences. It examines the mechanisms
disturbances, ranging from insomnia to non-restorative underlying the neurological manifestations of COVID-19,
sleep, also significantly impact quality of life and cognitive considering both viral and host factors. In addition, the
functioning. Despite its growing prevalence, the precise article explores current insights into how SARS-CoV-2
5-8
underlying mechanisms of long COVID remain poorly affects brain function and structure, drawing on recent
understood. research and emerging evidence. By synthesizing existing
findings and identifying knowledge gaps, this article aims
Recent studies examining the cognitive effects of long to provide a comprehensive overview of COVID-19’s
COVID have revealed deficits in global cognition as well as neurological implications and guide future research in this
specific cognitive domains. For instance, a multicenter critical area.
9,10
study found significant cognitive slowing in patients with
post-COVID conditions. Similarly, a large observational 2. The neurological impact of SARS-
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study conducted in England documented more severe CIs CoV-2: From acute infection to post-acute
in COVID-19 survivors, particularly among those infected sequelae
with early variants or those who had been hospitalized.
12
Neuropsychological evaluations conducted several months The neurological impacts of SARS-CoV-2 extend beyond
post-infection have identified declines in memory recall, the acute infection phase, manifesting in a wide range of
executive function, and processing speed. However, the symptoms during the post-acute sequelae of SARS-CoV-2
13
short follow-up periods in these studies underscore the infection (PASC) (Table 1). These effects are observed
need for extended research to better understand these across the spectrum of illness severity, and while the
CIs. 10-12 Moreover, approximately 35% of patients developed exact mechanisms remain unclear, research is uncovering
neurological or psychiatric complications within 6 months patterns of persistent neurological and psychiatric
of infection. Although similar neurological complications disturbances. This section elaborates on the acute and
14
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have been observed following other respiratory infections, long-term impact of COVID-19 on the nervous system,
the specific pathophysiology and long-term consequences focusing on symptom prevalence, risk factors, and the
of COVID-19-related neurological effects remain broader implications for public health.
unclear. Multiple large-scale studies have demonstrated
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an association between COVID-19 and cognitive deficits, 2.1. Acute neurological symptoms and post-acute
including memory and concentration impairments during sequelae
the post-acute phase. Survey data from United States PASC refers to the persistence or emergence of new
working-age adults also indicated a growing incidence symptoms following the acute phase of the infection,
of memory and concentration difficulties linked to the affecting individuals across a spectrum of initial illness
virus. 16,17 severity, ranging from mild to critical cases. Early studies,
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SARS-CoV-2 primarily enters host cells through including those involving both hospitalized and non-
the angiotensin-converting enzyme 2 (ACE2) and hospitalized patients, have shown that nearly all participants

Volume 4 Issue 2 (2025) 13 doi: 10.36922/an.4909