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

214 patients, and all neurologic symptoms were reviewed Although thromboembolism resulting from a “cytokine
by two trained neurologists. In addition to all laboratory storm” is recognized as a contributor to the high morbidity
tests (complete blood cell count, blood chemical analysis, and mortality associated with COVID-19, the precise
coagulation testing, assessments of liver and renal mechanisms behind CAC and its role in ischemic stroke
function, C-reactive protein, creatine kinase, and lactate remain incompletely understood. 37,38
dehydrogenase), radiologic examinations were performed, In a study involving 8163 COVID-19 patients, 103
including head and chest computed tomography scans. developed acute ischemic strokes, often linked to underlying
Patients with severe COVID-19 infections were more conditions such as hypertension, diabetes, hyperlipidemia,
likely to develop neurologic manifestations, especially atrial fibrillation, and heart failure. COVID-19 triggers
acute cerebrovascular disease, conscious disturbance, and systemic coagulopathy and inflammatory responses,
skeletal muscle injury. In a cohort analysis conducted by leading to CAC, which increases the risk of ischemic
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Almeria et al., it was suggested that patients with the acute strokes. Serial histological analyses of 100 autopsies
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syndrome of COVID-19 showed lower scores in memory from COVID-19-positive patients revealed widespread
and attention, along with a reduced global cognitive microthrombi and microinfarcts in the neocortex of 58 brains,
index. Similarly, in a community-based cohort study, Jacot with microthrombi often linked to small, patchy infarctions.
de Alcântara et al., 2023 found that cognitive deficits Immunohistochemical staining also demonstrated robust
35
following SARS-CoV-2 infection were still detectable angiotensin-converting enzyme 2 (ACE2) receptor expression
nearly 2-year post-infection, particularly in individuals in intraparenchymal blood vessels. These findings align
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with prolonged symptoms, ongoing issues, or more severe with neurological symptoms such as headaches, altered
cases of the disease. In contrast, no cognitive deficits were senses, cognitive defects, and increased mortality. These
observed in individuals who reported full recovery from symptoms are attributed to neurocoagulation, resulting
COVID-19. The impact of ongoing symptoms was assessed from excessive thrombin generation and disrupted
using multivariable linear regression models, stratified BBB function. Post-mortem studies also suggest brain
by self-perceived recovery. In addition, a longitudinal endothelial injury in COVID-19 patients, likely caused by
analysis was conducted to evaluate changes in cognitive host defense mechanisms rather than direct viral presence.
performance over time. Moreover, a thorough regional 40
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mapping of the olfactory nerve tracts and adjacent CNS In a current finding, Douaud et al. examined 785 patients
regions in autopsy material from 33 COVID-19 patients from the UK Biobank and analyzed magnetic resonance
confirmed the presence of viral RNA in the cerebellum. 36 imaging data collected over 3.2 years from individuals who
had contracted COVID-19. Consistent with the frequent
COVID-19-associated coagulopathy (CAC) has been reports of smell and taste impairment in COVID-19, the
identified as a significant contributor to ischemic stroke in study found greater structural abnormalities and indicators
long-COVID patients. Evidence suggests that CAC arises of tissue damage in regions associated with the primary
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from intricate interactions between the innate immune olfactory cortex, including the anterior cingulate cortex,
response, coagulation and fibrinolytic pathways, and the orbitofrontal cortex, insula, amygdala, ventral striatum,
vascular endothelium, leading to a procoagulant state. hippocampus, and parahippocampal gyrus. Notably, the
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This perspective categorizes the current understanding of authors observed a marked reduction in the total brain
CAC into three main pathological mechanisms: volume, even in patients who had experienced only mild
(i) Vascular endothelial cell dysfunction: COVID-19 COVID-19 symptoms, suggesting a potential increase in
induces endothelial dysfunction, impairing the normal cognitive decline. Most brain imaging studies on COVID-
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function of blood vessels and promoting interactions 19 have focused on acute cases, examining individual
between the endothelium and immune cells, such as reports or small case series using computed tomography,
neutrophils positron emission tomography, or magnetic resonance
(ii) Hyper-inflammatory immune response: The imaging scans. These studies have revealed a range of
disease triggers a hyper-inflammatory response, brain abnormalities, including white matter changes,
marked by elevated levels of inflammatory markers reduced cerebral blood flow, and signs of ischemic events,
such as neutrophil gelatinase-associated lipocalin, especially in the cerebrum. 17,18,41 However, it is still unclear
contributing to a heightened procoagulant state whether these abnormalities predated SARS-CoV-2
(iii) Hypercoagulability: Unlike typical coagulopathy, infection. It is possible that these brain changes indicate
CAC is not driven by the usual thrombin-dependent pre-existing vulnerabilities that make certain individuals
coagulation factors but is instead characterized more susceptible to the effects of COVID-19 or more likely
by an abnormal coagulation response driven by to experience severe symptoms, rather than being a direct
SARS-CoV-2. result of the disease itself.

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