CNN – One of the most puzzling aspects of the new coronavirus is the number of organ systems affected during the course of the disease. We have heard about the heart, lungs, and respiratory symptoms, but a growing mystery is their impact on the nervous system.
An April report suggested that more than a third of the 214 Covid-19 patients studied experienced neurological complications ranging from loss of smell to stroke.
The virus can cause neurological complications such as delirium, brain inflammation, stroke, and nerve damage. In a University College London study published earlier this month, 10 of 43 patients had “temporary brain dysfunction” and delirium, while 12 had brain inflammation, eight had strokes, and eight had nerve damage.
Another article published last month in The Lancet Psychiatry examined 153 patients in the UK and found that even those under the age of 60 could have psychosis, depression, or stroke.
How this virus damages the brain and nerves is still not entirely clear. But as two doctors dedicated to the study of the nervous system, we wanted to find some answers.
Dr. Sanjay Gupta has been a practicing neurosurgeon for the past 20 years and has always been amazed at the remarkable ways the body protects the brain. A hard shell of bone, a bath of clear liquid, and a blood-brain barrier, which creates checkpoints before certain molecules can enter. It is our most important and most waterproof organ than most. And yet this virus can still sneak into the central nervous system.
And Dr. Minali Nigam is a newly-elected resident doctor and decided to enter neurology, a field that connects the mind and body. Seemingly small details like the ability to raise an eyebrow can tell us which part of the nervous system is injured. There is so much that we don’t know about the brain, which means tremendous potential for our knowledge to grow.
Coronavirus also affects the brain and nerves.
Among the most common neurological symptoms are loss of smell and taste, which could be the first clues that someone has Covid-19.
Other possible symptoms include headache, dizziness, loss of consciousness, weakness, seizures, paralysis, strokes, and more.
We know that the virus spreads through particles in the air, so it first enters the body through the nose and mouth. When this happens, the virus may potentially pass through the cribriform plate, the bone at the top of the nose, to reach the olfactory bulb that houses the olfactory nerve and its branches. If the virus damages these nerves, a person can lose their sense of smell. If the virus also directly invades the taste buds, it can prevent nerve fibers from transmitting signals to the brain and cause a person to lose their sense of taste.
Of course, that’s just a hypothesis, but from one study we know that up to 88% of 417 of Covid-19-positive patients had these types of symptoms. Most of them recovered in two weeks, with no ongoing neurological problems.
Another hypothesis has to do with a protein receptor called an angiotensin-converting enzyme, known as ACE2, which is found in cells throughout the body in the lungs, kidneys, blood vessels, muscles, nose, and mouth. In the nose and mouth, the virus is believed to bind to ACE2 receptors on sensory nerve cells and block these cells so they do not facilitate smell and taste.
ACE2 also helps maintain blood pressure and protects the heart and brain from damage. Its function is to reduce the levels of a molecule called angiotensin II. If angiotensin II levels build up, the blood vessels constrict and reduce blood flow to the organs, which could damage them.
Here is the most interesting thing we are starting to learn. Whether it’s the body or the brain, most symptoms don’t seem to come directly from the virus, but rather, the body’s jealous immune response to fight the virus.
“The story of how such a virus, with so little genetic information, can wreak havoc on our nervous system is truly fascinating,” said Dr. Majid Fotuhi, medical director of the NeuroGrow Brain Fitness Center and affiliated staff of Johns Hopkins Medicine.
Take punches, for example.
When the virus binds to ACE2 in the blood vessels, it triggers an immune response, sometimes called a cytokine storm. Too much inflammation can damage the body’s clotting system and form millions of small clots or several large clots. Along with the higher levels of angiotensin II that constrict blood vessels, clots can block blood flow to the brain and lead to a stroke.
Some strokes are mild, and patients may not realize they have one. As people age, multiple strokes can accumulate and cause memory loss or poor attention. According to Fotuhi, other patients recovering from Covid may show symptoms of their silent strokes such as depression, anxiety, insomnia, or cognitive decline later in life.
But make no mistake, these strokes are sometimes serious or fatal, even among healthy people in their 30s and 40s, according to doctors.
Too much inflammation can also break the protective wall known as the blood-brain barrier, causing brain inflammation, seizures, or spread of infection.
This is how Skylar Herbert, 5, the daughter of two Detroit first responders, might have developed brain inflammation from meningitis. She was the first Michigan girl to die of Covid-19.
It is unclear why he developed meningitis. But we know that the meninges are a protective layer around the brain and spinal cord and are rich in blood vessels and ACE2. Theoretically, if the virus binds to ACE2 in the meninges, this could lead to damage to the blood vessels and significant inflammation.
Some patients with the virus were also found to have Guillain-Barré syndrome, a nervous disorder that can lead to paralysis. Here the antibodies, formed in response to the virus, react to the proteins found in the nerves, causing damage.
But it is important to remember that everyone responds to the virus differently.
“There are people who have a measured response to the virus and their immune system can control it without overreacting,” Fotuhi said.
“Healthy people who are asymptomatic are those who had enough immune response to destroy the virus without creating a storm of cytokines or blood clots.”
Because it is important
Neurological complications are not exclusive to Covid-19. Viruses like influenza, measles, respiratory syncytial virus, and Zika also have them, as do the other types of coronaviruses, SARS, and MERS.
The way this occurs comes down to two main mechanisms: direct viral invasion of the nervous system or damage to an overactive immune system.
Some neurological manifestations such as confusion or weakness can also be nonspecific complications of critical illnesses that are not related to the actual virus.
“Neurological involvement appears to be a prominent feature of this particular coronavirus,” said Dr. Felicia Chow, an expert in neuroinfectious diseases at the University of California, San Francisco.
Or we may be seeing more neurological complications with Covid simply because there are far more cases of Covid overall compared to previous coronavirus outbreaks.
Like what doctors see with Covid-19 and strokes.
“What has been reported so far is not really something that we commonly see with at least certain types of respiratory viruses,” he said. “But it is difficult to say with the still limited information we have. It takes a much deeper dive to understand the true neurological burden and the aftermath of this pandemic.”
There are no large studies looking at Covid-related neurological symptoms, so doctors are currently treating these symptoms as they would be for patients who do not have the virus.
But little studies have come out with a few hundred people. A consistent feature is that patients with risk factors such as high blood pressure, diabetes, and obesity who contract Covid are at greater risk of serious outcomes, including neurological complications, than healthy and fit people.
This is why regular exercise, a healthy diet, adequate sleep, and stress reduction remain important during this pandemic. By maintaining an active and healthy lifestyle, patients who end up infected can “improve their chances of a faster and more favorable recovery,” Fotuhi said.
For doctors, Covid patients may not be sick with the typical viral symptoms you’d expect, such as a cough or fever. Some patients who present in the emergency room have only shown signs of stroke. And brain symptoms may be the patient’s first and only symptoms. In certain situations, blood thinners and steroids can be just as important as antiviral medications.
“Covid can have many different faces,” said Fotuhi. “It is important that people appreciate that.”
And it is something that we will take into account when caring for patients.
By covering the pandemic as journalists and serving Covid patients as doctors, we have learned to keep an open mind. What we think today may change tomorrow and that is fine. It is part of the learning process. As our knowledge of the virus continues to grow, we are one step closer to persevering together in this pandemic.
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