In a recent study published in Brain Research Bulletin, researchers reviewed the neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Study: Nervous system manifestations related to COVID-19 and their possible mechanisms. Image Credit: Magic mine/Shutterstock
Background
SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), enters host cells by binding through its spike (S) protein to the angiotensin-converting enzyme 2 (ACE2). Besides respiratory symptoms, approximately one-third of patients with COVID-19 develop neurologic symptoms. Reports suggest that 88% of patients with severe COVID-19 show neurologic symptoms. In the present study, researchers discussed the effects of COVID-19 on the nervous system.
Infection of the nervous system
SARS-CoV-2 could affect the nervous system in two ways, direct invasion or systemic effects. While most studies reported that ACE2 expression is confined to the smooth muscle and endothelial cells of cerebral blood vessels, growing evidence suggests that ACE2 and transmembrane protease serine 2 (TMPRSS2) expression might occur at low/baseline levels in the brain. It is, therefore, possible that SARS-CoV-2 could directly infect nerve cells.
Alternatively, peripheral nerves might allow SARS-CoV-2 invasion of the brain via the retro-neural route. It has been speculated that the afferent parts of trigeminal, olfactory, vagus, and glossopharyngeal nerves might permit viral spread from the surroundings to the central nervous system (CNS).
Neurologic disorders involving SARS-CoV-2 infection
Evidence indicates that the incidence of ischemic stroke among COVID-19 patients is 5% to 6.9%. Ischemic stroke can occur in older adults with pre-existing comorbidities and younger adults without any apparent history of comorbidities. Cerebral venous thrombosis (CVT) is rare and occurs in about 0.3% of COVID-19 patients.
One study reported that 5% to 15% of patients with severe disease developed arterial or venous thromboembolic complications. Patients without any predisposing factors for congenital CVT could develop thrombosis and hypercoagulability due to COVID-19. Clinically, COVID-19-induced CVT does not significantly differ from CVTs caused by other coagulopathies.
Neurologic disorders due to direct infection
It has been estimated that up to 28% of patients with COVID-19 with at least one neurologic manifestation develop encephalitis. A hospital in Beijing reported the first case of CNS infection by SARS-CoV-2, confirmed by genetic examination of cerebrospinal fluid (CSF). Symptoms, CSF examination, and imaging of this case were similar to those observed in meningoencephalitis.
Others have also documented meningoencephalitis during COVID-19 and reported greater brain damage caused by immune inflammation than by SARS-CoV-2 infection. Anosmia and ageusia are common in COVID-19 patients, observed in over 85% and 88% of cases. It is believed that SARS-CoV-2 infects olfactory and tongue epithelial cells resulting in the loss of smell and taste.
Some researchers have theorized that the loss of sensory olfactory neurons, possibly by inflammation-associated apoptosis, supportive cell dysfunction, or direct viral invasion, might cause anosmia. Loss of taste/smell persists for about ten days, and patients usually recover within four weeks of diagnosis.
Immune abnormalities- and inflammation-driven neurologic symptoms
Infection-induced immune abnormalities and excessive inflammation cause a variety of neurologic disorders. In the case of COVID-19, one study involving over 2500 participants documented acute necrotizing encephalopathy (ANE) in four patients, limbic encephalitis in nine individuals, and acute disseminated encephalomyelitis (ADEM) in 13 subjects, facial paralysis in two cases, critical illness myopathy in six patients.
ANE, a rare disease, is characterized by damage to the brain. Typically, symmetrical multifocal lesions and thalamic involvement are observed in imaging analysis. ADEM is another rare inflammatory condition affecting the spinal cord and brain, usually in children. It is associated with post-infection inflammation and immune abnormalities, and imaging and autopsy findings showed features similar to other ADEMs.
Autoimmune encephalitis is uncommon in COVID-19 patients, but clinically, it is similar to that observed in non-infected patients. Myalgia is common among COVID-19 patients and is documented in up to 64% of cases. Severe COVID-19 patients might be at an elevated risk of muscle damage than mild/other cases. Rarely, muscle damage and myalgia could lead to rhabdomyolysis.
Other neurologic disorders due to COVID-19
In a survey of around 11,000 COVID-19 patients, researchers identified two cases of myasthenia gravis (MG) and neuromyelitis optica spectrum disorders (NMOSD). A study on MG patients reported that only 0.96% contracted SARS-CoV-2, and most individuals developed severe COVID-19 requiring intensive care and mechanical ventilation.
While dementia, Parkinson’s, and Alzheimer’s disease are less prevalent among COVID-19 patients, brain fog is frequent, with an estimated incidence of 81%. Brain fog causes memory problems and inability/difficulty focusing. Besides, mental complications such as anxiety, depression, and post-traumatic stress disorder (PTSD) are common post-COVID-19.
Nearly 4.6% of patients with no history of pre-infection mental illness could develop a new anxiety disorder within three months of COVID-19 diagnosis. The incidence of anxiety disorders, depression, and PTSD is 34.7%, 28.5%, and 96.2%, respectively. Additionally, because of the COVID-19-induced social isolation and lockdowns, drug abuse, suicidal thoughts, and mood disorders have increasingly become prevalent.
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