BRAIN AT RISK WITH COVID-19
Experts examine the neurological impact of virus
He's not waking up. Why isn't he waking up? doctors wondered.
Torry Robertson had beaten the odds. He had survived the worst that COVID-19 can do — blood oxygen so low that he needed a ventilator to breathe, encephalitis or inflammation of the brain, cerebral hemorrhaging, inflammation in his heart causing low blood pressure, kidney failure, blood clots, blood infections, COVID pneumonia, bacterial pneumonia.
Finally, after Robertson had overcome the acute illness, doctors began cutting back his myriad medications, including sedatives administered when he was connected to the ventilator.
But Robertson, a 46-year-old nurse from Lasalle, remained unresponsive.
That's when doctors at Windsor Regional Hospital became concerned about the virus' impact on his brain.
It's called an “altered level of consciousness,” and it's the first neurological symptom of encephalitis from viral illness, according to a case study at Western University's Schulich School of Medicine and Dentistry in London, published in Neurology Clinical Practice in July.
Robertson was ultimately diagnosed with severe and extensive hemorrhagic encephalopathy. Encephalopathy is a general term for brain injury. The damage was likely caused, at least in part, by the inflammation, which is also believed to have caused bleeding in his brain.
Hundreds of studies around the world, beginning early in the pandemic and continuing, document neurological abnormalities in COVID-19 patients.
As many as 70 per cent of COVID-19 patients experience neurological injuries, estimates Robertson's neurologist, Dr. Michael Winger. Most are mild, such as headaches, confusion and memory loss. Even loss of taste and smell signals damage to a nerve that goes to the brain.
Robertson is an extreme example. Less than five per cent of patients get encephalitis, Winger estimated.
That sounds like a small number. Until you consider this. More than 52 million people around the world have been infected with COVID-19. Among those who are sick enough to be hospitalized, the number suffering from more severe neurological problems is higher.
“I probably saw four patients with similar problems to Torry's,” Winger said, “so it's not rare.”
And neurological damage can occur even in young, otherwise healthy patients, like Torry, and those with mild cases of the virus. There may be people who are infected with COVID-19 but don't have symptoms, are never tested and develop neurological problems. Severe damage, like Torry's, is clear. You can see the lesions on an image from an
MRI. But there could also be subtle changes in the nervous system that aren't immediately apparent.
We also don't know why some people have neurological damage and some don't or who is most at risk.
It could all add up to an epidemic of neurological problems requiring continuing care. The implication is huge.
“Oh, it is,” said Winger. “(COVID-19) can cause encephalomyelitis (inflammation of the brain and spinal cord), it can cause strokes, it can cause seizures, it can cause spinal cord damage, nerve damage in the arms and legs.
“When you look at it, you realize, what can't it do?
“COVID has become part of our differential for people who present with (neurological) symptoms,” he said. “You're healthy. You had a seizure. We better COVID test you. You have new onset headaches. Maybe we better get a COVID test.”
The damage to Robertson's brain is deep in the organ, in an area called the basal ganglia, between the temporal lobes behind the ears. It affects both sides of his brain.
This is where injury is typically seen in COVID-19 patients. The untrained eye can see the damage on an MRI image, dark spots on white matter and white spots on dark matter.
“His MRI images are very, very classic,” said Winger.
It affected Robertson's ability to process information, to talk, to walk. This, again, is what is expected when the basal ganglia is damaged. He also had difficulty swallowing, something the brain also co-ordinates.
The biggest question is, how does the virus damage the brain? There are two theories. The first is that it's collateral damage.
“Clearly COVID does something to our immune system,” said Winger.
Many experts and studies cite an autoimmune reaction. Some patients' immune systems overreact to the viral infection, producing inflammation that is so severe that it's life threatening. It can happen anywhere in the body, including the brain.
It could also be a low level of oxygen in the blood, which is common in COVID-19 patients. Some patients have low oxygen but show no signs of distress, a condition dubbed happy hypoxia. Or patients can also become prone to blood clots that block the flow of oxygen or to hemorrhaging. It could be the combined assault throughout the body of all the many and varied complications.
The second theory — and evidence is emerging to support it — is that the virus attacks the brain directly.
Studies have shown that a spike protein on the virus can attach to a protein on the surface of other cells called ACE2 and invade and infect them.
The brain, as Winger says, is a “very privileged” place. It's protected by something called the blood-brain barrier that is designed to keep pathogens out of it. This barrier is made up of cells called endothelial cells, which line the blood vessels. Until recently, according to studies from Yale and Temple universities, it wasn't clear whether ACE2 is present in the brain. But the studies from Yale and Temple show that it is and that the virus' spike protein appears to trigger inflammation in the endothelial cells, making the barrier “leaky,” according to the study from Temple.
“Our results suggest that the neurologic symptoms associated with COVID-19 may be related to consequences of direct viral invasion of the CNS (central nervous system),” states the Yale study.
“It's hard to prove that the COVID virus infects the brain,” said Winger. But, he said, “it may well affect the lining of the blood vessels. If the blood-brain barrier gets leaky, then anything in the bloodstream can pass right into the brain.”
The cerebrospinal fluid in some of Winger's severe COVID patients has been tested for evidence of the virus. None has been found. However, it was found in the cerebrospinal fluid of a patient in Japan, according to a case report in the International Journal of Infectious Diseases in March.
Winger is not aware of any of the brains of severely ill COVID-19 patients in Windsor being biopsied, but traces of the virus were found in the brain cells of patients in Germany, according to an article in The Lancet Neurology this month.
Other case studies have also found evidence of the virus in cerebrospinal fluid and in the brain.
“It's really hard to sort it out,” said Winger. “I don't think it's a single problem. I think there are lots of things that go wrong in a patient with COVID. I think COVID affects the entire body.”
Other viruses can affect the brain. Does COVID affect the brain more than other viruses? That's not clear. But there is something that makes COVID-19 very different from other viruses.
“Certain viruses affect the brain,” said Winger, “but COVID, in terms of affecting the entire body, is incredibly unique. Nothing else does this. SARS doesn't do this. H1N1 doesn't do this, not on this scale.
“If it was a documentary on TV, it would be fascinating. But when you have to live through this...”
The next big question is, how long do COVID-19'S neurological symptoms last?
We don't know. But we do know that even mild effects, like “brain fog” that some patients here and around the world describe, can last months.
And what happens as patients age? Winger asked. Again, we don't know. Winger compared it to a concussion. You can recover from a concussion but be prone to other neurological problems years later.
“We don't know what a COVID infection could cause five, 10, 15 years down the road,” he said. “There's no predicting what's going to happen. That is something that is of concern.”
In Robertson's case, it's a question of how much of his brain is permanently damaged and how much is injured and has the potential to recover.
When he left acute care last July, he still had difficulty waking up and staying awake. Keeping him conscious was the first goal when he began rehabilitation.
Now, he wakes up in the morning, feeds, showers and dresses himself with minimal assistance. But he still has difficulty processing information, speaking and swallowing. He walks with a walker. His progress has been utterly remarkable. But he continues rehabilitation, and it will be a long and slow. While much of recovery happens in the first six months, it can take a year, two years, even longer. And there are no guarantees.
“He's a younger, healthy male. He didn't have other problems. So we're optimistic he's going to continue to recover,” said Winger. “How much? I can't predict.”
But in another example of how unpredictable COVID-19 can be, Robertson has already defied the odds. Winger had four patients with severe brain damage like Robertson.
“Torry was the only survivor,” he said. “Most patients die, in my experience here. It's a very poor prognosis. Torry's recovery has been incredibly uplifting and gratifying.”
I think there are lots of things that go wrong in a patient with COVID. I think COVID affects the entire body.