What Does Coronavirus Do to the Brain?

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Why do younger people with a healthy immune system sometimes succumb to novel coronavirus? Insights from studies of novel coronavirus point to the possibility that the virus may shut down breathing by infecting the brain.

The vast majority of people infected with novel coronavirus, or SARS‐CoV‐2, experience only mild to moderate symptoms or no symptoms at all. Reported mild to moderate symptoms of COVID-19—the illness caused by the virus—include fever, dry cough, loss of smell and taste, sore throat, leg pain, headache, stomach ache, diarrhea, and fatigue. In more severe cases, patients present with pneumonia and severe difficulties breathing (dyspnea). A small fraction of people become so gravely affected that they require a ventilator to help them breathe.

While the elderly and people with an underlying medical condition are at a higher risk of developing serious symptoms and dying from novel coronavirus, younger people without any known pre-existing condition have also succumbed to severe forms of the viral disease. This raises the question: What—besides a compromised immune system—can cause infected individuals to develop severe symptoms?

It is now known that coronaviruses can invade the central nervous system and cause damage to nerve cells in the brain. Studies from 2002 and 2003 that looked at samples from patients with classic SARS, the coronavirus that caused the 2003 SARS outbreak, found virus particles inside brain cells, including the cells in the brainstem that regulate breathing.

It is less clear how coronaviruses enter the brain. Classic SARS and novel coronavirus have a very similar genetic structure and mechanism for invading human cells. Indeed, classic SARS and novel coronavirus use the same hook to attach themselves to human cells. In the respiratory system, including the nose, throat, and lungs, the invasion of human cells is mediated by a protein called ACE2, which is also expressed in the small intestine, the kidneys, the pancreas, and the lining of blood capillaries.

But ACE2 is not expressed in brain cells, which suggests that the virus enters the brain from somewhere else in the body. Almost no virus particles have been found in the brain fluid outside of brain cells, which rules out that the virus enters the brain via the blood or through lymph notes. The most likely source of the virus particles found in the brain thus appears to be the respiratory system.

Studies of the classic SARS coronavirus in mice lend evidence to this hypothesis. In these studies, it was found that when infection occurs through the nose, the virus can enter the brain through the nerve cells used to process smell (olfactory nerves). From here, the virus can spread to the brainstem and destroy the brain cells responsible for breathing.

Although this hypothesis has not been confirmed for novel coronavirus, the high similarity between classic SARS and novel coronavirus indicates that novel coronavirus could also cause respiratory distress and death by destroying the areas of the brainstem that control breathing. Indeed, one study found that almost half of patients with severe respiratory symptoms from COVID-19 also had neurological symptoms, including stroke, brain hemorrhage, and impaired consciousness.

Together this body of evidence suggests that when novel coronavirus results in serious illness and death, this may occur due to a secondary infection of the brainstem through the nose, which can then shut down breathing.