We're only just beginning to learn how Covid-19 affects the brain

One of the more puzzling aspects of the novel coronavirus is just how many organ systems are impacted through the course of the disease. We've heard about the heart, lungs and respiratory symptoms, but a growing mystery is its impact on the nervous system.

A report suggests more than a third of 214 Covid19 patients studied experienced neurological complications ranging from loss of smell to stroke. The virus can lead to neurological complications like delirium, brain inflammation, stroke and nerve damage. In a University College London study published earlier this month, 10 out of 43 patients had "temporary brain dysfunction" and delirium, while 12 had brain inflammation, 8 had strokes and 8 had nerve damage.

Another paper published last month in The Lancet Psychiatry looked at 153 patients in the UK and found even those younger than 60 could have psychosis, depression or strokes. How this virus damages the brain and nerves still isn't clear.

The brain is remarkably protected by the body. A hard shell of bone, a bath of clear fluid and a blood brain barrier, which creates checkpoints before certain molecules are even allowed to enter. It is our most important organ and more impervious than most. And, yet this virus is still able to sneak into the central nervous system.

Coronavirus affects the brain and nerves, too

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 the virus spreads through particles in the air, so it first enters the body through the nose and mouth. When this happens, it's possible the virus then potentially crosses 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 taste buds, it can prevent nerve fibers from transmitting signals to the brain and cause a person to lose their sense of taste.

That's just one hypothesis. Another hypothesis has to do with a protein receptor called angiotensin converting enzyme -- known as ACE2 -- which is found in cells all over the body in the lungs, kidneys, blood vessels, muscles, nose and mouth. In the nose and mouth, the virus is thought to bind to ACE2 receptors in sensory nerve cells and block these cells from facilitating smell and taste.

ACE2 also helps maintain blood pressure and protects the heart and brain from damage. Its role is to lower levels of a molecule called angiotensin II. If angiotensin II levels build up, blood vessels constrict and reduce blood flow to organs, potentially damaging them. Here is the most interesting thing we are starting to learn. Whether it is the body or the brain, most symptoms don't seem to come directly from the virus, but rather, the body's overzealous immune response to fight the virus.

"The story of how such a virus, with so little genetic information, can wreak havoc to our nervous system is really fascinating," says Dr Majid Fotuhi, medical director of NeuroGrow Brain Fitness Center and affiliate staff at Johns Hopkins Medicine.

Take strokes, for example. When the virus binds to ACE2 in blood vessels, it triggers an immune response -- sometimes referred to as a cytokine storm. Too much inflammation can impair the body's clotting system and form millions of small clots or several large clots. Together 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 minor and patients may not realise they are having one. As people age, multiple strokes could build up and cause memory loss or poor attention. Sometimes these strokes are severe or deadly -- even among people in their 30s and 40s.

Too much inflammation can also break down the protective wall known as the blood-brain barrier and lead to brain swelling, seizures or spread of infection.

It's 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 manage it without overreacting," Fotuhi says. "Healthy people who are asymptomatic are the ones who had just enough immune response to destroy the virus without creating a cytokine storm or blood clots."

Why it matters

Neurological complications aren't unique to Covid-19. Viruses like the flu, measles, respiratory syncytial virus and Zika have them, too, as do the other types of coronaviruses, SARS and MERS. How this happens boils down to two main mechanisms: direct viral invasion of the nervous system or damage from a hyperactive immune system.

Small studies with a few hundred people point to one consistent feature; patients with risk factors such as high blood pressure, diabetes and obesity who get Covid are at higher risk for severe outcomes, including neurological complications, than healthy and fit individuals.

That's why regular exercise, healthy diet, proper sleep and reducing stress are important during this pandemic. By maintaining an active, healthy lifestyle, patients who end up getting infected can "improve their odds of a faster and more favourable recovery," said Fotuhi.

For doctors, patients with Covid may not be sick with the typical viral symptoms you'd expect like cough or fever. Some patients who show up in the emergency room have only shown signs of stroke. Brain symptoms could be a patient's first and only symptoms. In certain situations, blood thinners and steroids may be as important as anti-viral medications. "Covid can have many different faces," Fotuhi said. "It's important for people to appreciate that."

In covering the pandemic as journalists and caring for Covid patients as doctors, we've learned that what we think today may change tomorrow. As our knowledge of the virus grows, we're one step closer in persevering through this pandemic together.( CNN)