Can COVID-19 cause neurological damage?

The patient, a woman, mentioned a strange, uncomfortable tingling, like pins and needles, almost a burning sensation, that shot down one side of her neck, one shoulder, one arm, and one side of her torso. The sensation had come out of the blue after a bout with COVID-19.

“She couldn’t quite predict where she was going to be feeling it,” said Serena

Spudich, chief of neurological infections and global neurology at Yale University School of Medicine, who first started hearing of the strange symptoms two months ago.

Spudich, who has spent most of her career, until now, studying HIV and how it affects the brain, mentioned the strange, patchy neuropathy or nerve damage, on a few webinars attended by doctors across the United States.

Neuropathy normally affects the longest nerves first, so the feet and hands. People later emailed Spudich. “Someone said she had experienced exactly this; another said, ‘ I have a patient that is experiencing that.’’’

For all the information she could get, it didn’t happen in the acute phase, when people are first infected. It started several weeks later. “It’s not dangerous in the sense that people are going to necessarily be falling over” or have trouble breathing, Spudich said. “But it’s a frightening sensation for somebody who has never had any kind of neurological disease before.”

Others infected with COVID- 19 arrived at the Yale emergency department complaining of confusion or problems concentrating. Their thinking was muddled, their “mental status” out of whack. Some arrived with severe headaches. Colleagues at other hospitals have reported strokes and seizures in the COVID-19 infected. One Detroit hospital reported a case of a 58-yearold airline worker whose CT and MRI scans showed abnormal brain lesions and a damaged thalamus. She couldn’t answer any questions beyond giving her name.

As COVID-19 simmers, a new question is emerging: Can the pandemic virus attack the brain?

“There is growing evidence of neurological complications and disease in patients with COVID- 19,” Spudich and colleagues wrote in a new paper published online in JAMA Neurology.

Still unclear is whether the virus itself is invading the central nervous system and brain, or whether the symptoms are the consequence of inflammation in the brain caused by an immune response run amok.

“The bigger concern here is, if there has been some kind of virus entry into the brain, does it have long-lasting effects?” Spudich said. “We just don’t know.”

A separate article published in the same journal suggests the virus is, in fact, gaining entry to the brain.

For months, loss of smell ( anosmia) had been anecdotally linked to COVID-19. Italian doctors report the case of a 25- year- old radiology worker who suddenly lost her sense of smell after becoming infected with the COVID-19 virus

An MRI scan showed what looked like inflammation in the gyrus rectus, the very front part of the brain involved with smell, as well as the olfactory bulbs, the main nerves responsible for ferrying smell from the top of the nose into the brain — suggesting, as Scientific American reported, that “SARS- COV- 2 had entered the patient’s nose and made its way to the nearest brain region from there.”

No brain abnormalities were seen in two other COVID-19 patients who also lost their sense of smell. However, co-author Letterio Politi told the magazine his team hypothesizes that the virus replicates in the moist tissues that line the nose, enters the olfactory bulbs and then reaches the cortex “trans-synaptically,” moving, like stones skipping across water, from one neuron to the next.

Loss of smell and taste have been reported so frequently in people infected with COVID-19 that King’s College London researchers last week said adding loss of smell and taste to the list of traditional COVID-19 symptoms (such as high fever and a continuous cough) would trace 16 per cent of cases that otherwise would be missed. This was based on data from tens of thousands of users from a COVID Symptom study app who have tested positive. Loss of taste and smell, the researchers wrote in The Lancet, was the strongest predictor of having the virus.

Most cases of smell loss are transient; smell, or taste come back. As well, Spudich’s patients who have reported that strange tingling and numbness in different parts of their bodies seem cognitively completely normal.

But there are concerns COVID-19 could be “neurotropic,” meaning toxic to the spinal cord and brain, and therefore lead to lingering brain complications.

One autopsy study found particles of the SARS- COV-2 virus in the neurons of a specimen of frontal lobe, Spudich and her colleagues report in their review. “Neurons were found to have viral particles packed in dilated vesicles” and, once the virus gets into neuronal tissue “it could begin a cycle of viral budding,” inflicting further damage to neurons.

Besides the olfactory bulb, the virus could be gaining entry into the brain by crossing the blood- brain barrier, or through the cribriform plate, a section of skull at the top of the nose with tiny holes that allow nerves to pass through.

But the virus may be addling the brain without getting inside it.

Normally, the brain doesn’t have much inflammation. “There’s not a lot of inflammatory mediators floating around,” Spudich said. But bring in a pathogen, a virus or bacteria, and the brain responds, signalling to the immune system, “invader.” More immune cells are invited into the brain, “and when you get a lot of immune cells into the brain, they release different chemicals and proteins that cause dysfunction,” she said.

Still, one unpublished paper reported finding neurons in the brain that carry receptors for a protein called ACE2, which the coronavirus uses to latch to and invade human cells. Another paper, this one of high- resolution imaging of brain tissue taken from someone who died of COVID-19, found the presence of virus in neurons.

“It’s really hard to make firm conclusions based on one or two autopsies,” Spudich cautioned.

It’s possible some people have a much higher loading of virus that makes it more likely that it’s going to enter the brain, she said.

“I think we have to be really careful here,” Spudich said. A lot of what doctors are seeing, neurologically, has happened in people who were severely sick with COVID- 19, she said. Confusion and altered mental states could be the result of low oxygen, or delirium associated with intensive care.

However, a survey by a support group for people experiencing prolonged symptoms of COVID-19 say neurological symptoms like brain fog, concentration problems, memory loss, dizziness and trouble sleeping were among the top symptoms reported consistently over eight weeks.

growing evidence of neurological ... disease.