The coronavirus mainly attacks the lungs, but also the kidneys, heart, liver and blood vessels. Clinical data to date indicate that COVID-19 is associated with neurological and neuropsychiatric disorders.
A study carried out with 500 hospitalized patients with COVID-19 showed that between 40 and 60% experienced headaches, confusion, delirium, or memory loss, suggesting that the virus may also attack the brain. In very sporadic cases, psychosis not associated with the severity of the disease have been described.
Not all of these symptoms have to be caused by the invasion of the virus into brain cells. They can be the result of widespread inflammation throughout the body. For example, inflammation of the lungs can release molecules that make the blood sticky and clog the blood vessels, leading to strokes.
Additionally, many neurological symptoms can be the result of cytokine storm and overstimulation of the peripheral immune system affecting the brain. We need to clarify the pathways by which the virus affects the brain through inflammation or infection, as the treatments could be different.
Neuroinvasion is rare
The route of entry to the brain can be through the nasal cavity to the connection of the nervous system through the epithelium or olfactory nerve, or even through the eyes.
We know that SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) receptors and their coreceptors to invade cells. The virus can also reach the cerebral vasculature through the bloodstream by binding to the ACE2 receptor expressed on endothelial cells in brain capillaries, crossing the blood-brain barrier, and invading and injuring the brain parenchyma.
Because the blood-brain barrier is disrupted in hypertension and hypertension is a common comorbidity of COVID-19, these patients may be at increased risk for brain complications.
Still, brain infection is rare, probably because neurons express few ACE2 receptors. Despite this, some people may be more susceptible due to a genetic background, a high viral load, or other reasons. It is necessary to study what are the predispositions by which neurological problems occur in COVID-19 patients.
Recent studies have confirmed that ischemic stroke, cerebral venous thrombosis and cerebral hemorrhage are common in elderly patients with COVID-19, but would represent only 1 to 5% of hospitalized patients. In a study by the General University Hospital of Albacete, it was determined that 1.4% of patients with COVID-19 had cerebrovascular problems with high morbidity and mortality.
In other cases, various neurological conditions such as encephalitis have been observed, and in more exceptional cases Guillain-Barré syndrome, anxiety and post-traumatic stress.
SARS-CoV-2 damage to the brain is being studied in animal models, in organoids – miniature brains grown in vitro – or in the autopsy brains of COVID-19 patients. In the latter, it was observed by means of electron microscopy or immunohistochemical techniques how the virus invaded neurons.
A sophisticated neuroinvasion system
The coronavirus has a sophisticated neuroinvasion system, it explodes the machinery of brain cells to multiply, but does not destroy them. Instead, it causes an inflammatory cascade and damage to neurons. SARS-CoV-2 infection appears to rapidly decrease the number of nerve synapses, the connections between neurons, but we have no clinical evidence whether this is reversible or not.
Researchers at Yale University (USA) have shown that neuronal infection can be prevented by blocking ACE2 receptors with antibodies or by administering cerebrospinal fluid from a patient with COVID-19. More research is needed to be able to design new strategies to block viral infection, and SARS-CoV-2 neurotropism cannot be ruled out.
Long-term consequences
The long-term health consequences of the effects of COVID-19 cannot now be estimated, so we must avoid each infection to reduce its effects after recovery. Neurological sequelae in recovered COVID-19 patients pose one of the greatest long-term threats.
Cases of degradation of the protective layer that protects neurons, myelin, have already been observed in recovered COVID-19 patients. The deterioration of the myelin layer is associated with important neurodegenerative diseases such as multiple sclerosis.
There is much more evidence that associates other viral brain infections with a higher prevalence of neurodegenerative diseases such as Alzheimer’s or aárkinson, so that in the future we could detect a higher incidence of neurodegenerative disorders in patients previously affected by COVID-19.
The Lancet magazine published the first probable case of a 45-year-old patient who, after recovering from COVID-19, began to develop Parkinson’s symptoms. More longitudinal follow-up studies will be needed to determine the long-term neurological and neuropsychiatric consequences of this pandemic.
Sonia Villapol, Assistant Professor, Houston Methodist Research Institute
This article was originally published on The Conversation. Read the original.
