COVID-19 Neurological Effects: Does Virus Directly Attack the Brain?

June 03, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's  Coronavirus Resource Center.

Neurologic effects can be a significant part of COVID-19, but does the SARS-CoV-2 virus directly damage the central nervous system or are the neurologic symptoms attributable to secondary mechanisms? 

A new review article summarizes what is known so far, and what clinicians need to look out for.

"We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response — a bystander effect of people being severely ill. It is probably a combination of both," senior author Serena Spudich, MD, Yale School of Medicine, New Haven, Connecticut, told Medscape Medical News.

"Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences," she said. 

The review was published online May 29 in JAMA Neurology.

Brain Changes Linked to Loss of Smell

In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell — the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.

"Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway," conclude the researchers, led by first author Letterio S. Politi, MD, IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.

Spudich described this case report as "compelling evidence suggesting that loss of smell is a neurologic effect."

"Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement," Spudich commented. "While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects," she added.

In their review article, Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.

"We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects," she said. "There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain."

Spudich is a neurologist specializing in neurologic consequences of infectious disease. "We don't normally have such vast numbers of patients but in the last 3 months there has been an avalanche," she says.

From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.

"Reports from China suggested that serious neurologic effects were present in about one third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that ­— maybe around 10%," she notes.

Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Spudich reports. "Medical staff need to be aware of this — a severe headache in a patient who doesn't normally get headaches could be a sign of the virus."

Some of the neurologic symptoms could be caused by autoimmunity. Spudich explains that in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. "This is well described in HIV, but we are also now seeing this in COVID-19 patients too," she says. "A panoply of conditions can be caused by autoimmunity."

On the increase in strokes that has been reported in COVID-19 patients, Spudich says: "This could be due to direct effects of the virus (eg, causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway."

There have been some very high-profile reports of younger patients with major strokes, she said, "but we haven't seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven't seen a preponderance of strokes in young, otherwise healthy people."

Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.

"We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don't know where in this [cluster] COVID-19 virus falls," Spudich said.

"The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging."

She urges clinicians to try to collect such information in patients with neurologic symptoms.

Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Spudich suggests that some changes in procedure may help. "In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator."

It is also unclear whether the neurologic effects seen during COVID-19 infection will last long-term.

Spudich notes that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. "This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this," she said.

JAMA Neurol. Published online May 29, 2020. Review, Case report   

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