Doctors Struggle To Learn If, And How, COVID Affects The Brain

Six months into the COVID-19 pandemic, there is still much we don’t know about the disease.

But doctors around the world are racing to examine worrying reports of COVID-19 affecting the brain. Individual reports have shown strokes, brain swelling, and general brain damage occurring in patients with the disease, raising a serious question: Are the symptoms related to the viral infection? And, if so, how? 

“The key task of research is trying to determine whether there is a mechanistic, causal relationship,” Dr. Robert Stevens, an Associate Professor of Neurology and Anesthesiology Critical Care Medicine at Johns Hopkins School of Medicine who is running a study on the matter, told TPM.

The nature of the relationship between COVID-19 and brain conditions is unclear. Even the existence of such a relationship is debated.

“There’s good reason to infer that there might be some kind of indirect relationship,” Stevens added. “But if you want to interpret the data as currently available, it’s still speculative.”

While individual reports continue to stream in — many of them harrowing — doctors still don’t have enough big-picture data to provide firm answers on why these ailments are happening and on whether the virus really attacks the brain.

At the moment, most of the information about the neurological effects of COVID-19 comes in the form of case reports: write-ups of individual cases where a team of doctors observed something that might be indicative of a pattern.

Testing to figure out how widespread the problem is remains challenging. For one thing, it can be difficult to take samples of cerebrospinal fluid — the liquid that encases the brain and runs down the spine — from patients battling the disease. 

“It’s something of a challenge, especially when they’re very ill, to implement specific tests like getting a brain MRI, or a lumbar puncture to access the cerebrospinal fluid,” Stevens told TPM. “It’s not easy because the patients are so unstable that you could put them at risk by doing a lumbar puncture or taking them to the MRI to investigate.”

But across these case reports, some potential effects have become clear. More than half of COVID-19 patients lose their sense of smell, which could be indicative of an attack on the nervous system or on the brain itself. Some patients face more serious complications, including confusion and drowsiness. In worse cases, young, otherwise healthy people have had massive strokes, and there are indications that some patients may experience swelling in the brain.

It’s unclear which of these effects, observed in people with COVID-19, are related to the virus. And if they are, questions remain about which are caused by the virus directly, and which are caused by the body’s immune response to the disease.

Dr. Andrew Wilner, Associate Professor of Neurology at The University of Tennessee Health Science Center, told TPM that many of the disease’s “neurological symptoms” appear to be caused by the body’s response, saying that they seem to “occur by what we call indirect injury, which is due to being sick.”

One brain condition known as encephalopathy has been found to occur in up to 40 percent of serious COVID-19 patients. That presents as a collection of symptoms suggesting brain impairment, leaving patients confused and dizzy. In some more severe cases patients have experienced dementia.

That often occurs as patients suffer from severe respiratory issues, potentially slowing the flow of blood oxygen to the brain, and can persist even after the patient has been intubated and is on a ventilator.

The rub for researchers, however, is that encephalopathy tends to pop up with many severe viral infections. It’s not unique to COVID-19; rather, it tends to be a byproduct of serious illness. Just as when you’ve flown, you might get groggy — multiply that by 100. People get confused, and delirious, and “we see that all the time with non-COVID illness with critically ill patients,” Wilner told TPM. 

SERIOUS SYMPTOMS

What appears to be far more serious are reports of swelling of the brain — known as encephalitis — and strokes in those who also test positive for COVID-19.

The concern that COVID-19 may be related to strokes has been in the ether since doctors began to notice that those with the illness experience blood clotting.

But it was propelled further in late April by a case report out of New York City’s Mt. Sinai Health System, documenting five patients — all under the age of 50 — who had large-scale strokes while testing positive for COVID-19.

The lead doctor on the study, Thomas Oxley, described doing a procedure to remove the blood clot in the brain of the patient on a podcast hosted by the American Academy of Neurology. As he was doing the procedure, Oxley said, he was shocked to see the blood clotting around his medical instrument. 

“The interesting part and what makes this different is that strokes are occurring in people who would not otherwise get them,” said Wilner, adding that one hypothesis around why the strokes are occurring has to do with the blood clots linked to COVID-19, or with the virus attacking the blood vessel lining itself.

“But it’s impossible to make a generalization at this stage, because there are so many cases of COVID but so few with strokes,” Wilner added. 

It remains unclear the extent to which strokes and COVID-19 are a broader phenomenon related to the disease, beyond what was observed at Mt. Sinai.

STILL UNKNOWN: DOES IT INFECT THE BRAIN DIRECTLY?

Several case reports have been published suggesting other serious symptoms, which could be direct effects of the virus, or secondary effects resulting from the body’s response to the infection. 

Stevens, the Johns Hopkins researcher, told TPM that recent reports indicate a “signal” around inflammation of the brain and COVID-19, which could suggest early evidence of a link between the virus and encephalitis. 

One 74-year old Floridian man went to the ER after falling down twice, amid symptoms of fever and general confusion.

Doctors admitted the man to the hospital, where they found possible evidence of inflammation in his blood vessels, which could suggest encephalitis. He died after 11 days.

During an autopsy, researchers found traces of the coronavirus in his brain tissue.

A separate case report from Japan described a 24-year old who was found unconscious nine days after first coming down with headache, fatigue, and fever symptoms. The man survived and eventually awoke, but only after being found passed out, and after a series of seizures in the ambulance.

The man tested positive for COVID-19, with the virus — as well as evidence of brain inflammation — found in his cerebrospinal fluid, which is found in the brain and spinal cord. 

His case has been seen as suggestive of the virus entering the brain.

It remains unclear how common these cases are.

“It might be rarer or more frequent than we think it is,” Stevens said.

But he added that the seriousness of the brain-related symptoms — even in very rare cases — suggests that the disease would likely leave a population of survivors coping with long-term damage.

“All of these different neurological problems suggest that, at least for people who develop moderate or severe COVID-19, some of them at least are going to have some long-lasting sequellae, meaning that after they recover from respiratory failure, get off the ventilator, it’s likely that there are going to be some residual effects of the disease,” Stevens said, citing potential “cognitive impairments” and lung damage as things to watch out for.

“That means, unfortunately for some people who recover from this disease, they’re not out of the woods,” he added. “We’re talking about a disease that is complicated but may have lasting effects,” he said. “When we have a vaccine, there are still going to be people out there struggling with this long after it’s gone.”