SARS-CoV-2 infection typically affects the lungs, but studies have shown that other organ systems also experience damage. Damage to the neurological system following infection can even occur in patients with mild illness. 

Rates of neurological disorders

According to the results of a prospective, observational study published in Neurology, neurologic disorders were present in 13.5% of patients with COVID-19 during the study timeframe.

Frontera JA, Sabadia S, Lalchan R,  et al. A prospective study of neurologic disorders in hospitalized patients With COVID-19 in New York City. Neurology. 2021;96(4):e575–e586.

Many of these disorders occurred commonly in patients with critical illness. Of note, although Guillan-Barré syndrome was observed, encephalitis, meningitis, or myelitis secondary to SARS-CoV-2 infection did not occur. 

Ultimately, the relationship between SARS-CoV-2 and post-acute and long-term health effects should be considered in the context of infection-associated chronic illnesses. 

VA researchers who followed COVID-19 patients found that, despite a decline in post-acute sequelae by 2 years, the cumulative burden of health loss persisted in patients who had been either hospitalized or not hospitalized during the acute infection.

Bowe B, Xie Y, Al-Aly Z. Postacute sequelae of COVID-19 at 2 years. Nat Med. 2023;29:2347–2357.

The authors proposed that viral and nonviral diseases may result in post-acute and chronic disease, writing that “there is likely a bidirectional nexus between noncommunicable diseases and infectious diseases, in that noncommunicable disease[s] often increase the risk of infection and adverse outcomes after infection and that a viral infection may lead to the emergence of new-onset noncommunicable disease.” 

ACE-2

The relationship between the nervous system and SARS-CoV-2 is not yet well-established, but we know that the SARS-CoV-2 spike protein is highly attracted to the angiotensin-converting enzyme 2 (ACE-2) receptor and could be pivotal in neurologic pathology. 

“Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19,” wrote the authors of a literature review in the Journal of Integrative Neuroscience.

Ahmad SJ, Feigen CM, Vazquez JP, et al. Neurological sequelae of COVID-19. J Integr Neurosci. 2022;21(3):77.

“The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in [ACE-2] levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction.”

“Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to [hemorrhagic] stroke in patients with COVID-19,” they elaborated. “Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety.”

Calcium buildup

It is apparent that COVID-19 is associated with a wide range of neurological sequelae, including ischemic stroke, hemorrhagic stroke, peripheral nervous system disorders, disorders of cognition and memory, mental health disorders, migraines, seizures, and sensory disorders. One theory, according to the authors writing in ACS Omega, is that neurological function becomes compromised following infection with SARS-CoV-2 due to the antagonism of hydrogen bonding.  

Neurodegenerative risk factors include the presence of α-synuclein, amyloid β, or tau- also are rich in valine plus glycine residues. Aβ40 and Aβ42, two peptide fragments of amyloid β, possess nearly 30% valine plus glycine.  

“Together with long-COVID factors, they form extensive aggregates with calcium oxalate, compounding neurological and perhaps non-neurological symptoms,” wrote the ACS Omega authors. “Biochemical aggregates consisting of proteins and small, insoluble, and stiff molecules generate stresses and result in cell death.” 

Potential interventions

Remdesivir prevents viral replication, whereas dexamethasone is hypothesized to prevent neurological complications by mitigating hyperinflammatory organ injury.

Diet may also play a role in preventing the neurological sequelae of COVID-19, posit the authors in ACS Omega.

“Strong anions, for instance Cl–, antagonize calcium oxalate by disrupting secondary chemical bonding among proteins and insoluble salts and solubilize insoluble and stiff molecules,” they said. “To address changes in the proteome and sequelae of COVID-19, amino acids antagonizing valine plus glycine, for example, lysine or particular amino acids capable of hydrogen bonding, can be adopted in the dietary regimen at a modest amount to improve physical health.”