What does the coronavirus do to the nervous system?

Around the world, daily news reports cover three figures for the coronavirus: the number of people infected, the number of deaths and the number recovered.
 
What about those who avoid death – but who may be hit by a life-changing medical condition?
 
Many coronavirus patients are presenting early with neurological symptoms such as anosmia, ageusia and myopathy. In Italy, hospitals have been treating coronavirus patients who experience strokes, seizures and encephalitis-like symptoms, as well acroparesthaesia, according to the New York Times.
 
More evidence is emerging that the new coronavirus can affect the brain and nervous system, with neurological issues recorded in more than a third of coronavirus patients in an early case series from Wuhan published in JAMA Neurology.
 
But Dr Robb Wesselingh, a neurologist and researcher based at the Alfred Hospital, told newsGP this early study probably overestimates the chance of a coronavirus-linked neurological condition because its cohort was already very unwell.
 
‘A lot of these viruses can cause problems, but you need large numbers of infections because the neurological problems are the exception rather than the rule,’ he said.
 
‘After the Spanish Flu, there were at least 10 years of encephalitis lethargica, which was probably an immune-mediated encephalitis. So if you have millions infected with this coronavirus, it will still be a large number.
 
‘In the emerging literature, around 10–15% would have some sort of neurological effect. But if you account for all the mild cases, it will likely be less than 10%.’
 
Dr Wesselingh said that there are three main categories of neurological issues that could affect coronavirus patients.
 
#1: Neurological issues arising due to severe illness
The fact that the virus can cause blood clotting is emerging as a new cause for concern with the coronavirus, due to the heightened risk of stroke.  
 
‘The virus can have an effect on coagulation. The incidence of stroke is also much higher during the course of the disease,’ Dr Wesselingh said.
 
One cases series concerning him is a preprint Lancet study finding that strokes took place in 5% of coronavirus patients.
 
‘We’re seeing a lot more strokes. This isn’t only an acute issue – if antibodies are still present after the patient improves, strokes could still occur. We see this in lupus too,’ he said.
 
‘We’re not sure whether this will continue longer term. But in conversations with neurologists in the UK, it seems that even people with mild respiratory symptoms, there is a higher risk of strokes – for young as well as older people.’
 
#2: Direct viral invasion of the nervous system
One of the emerging tell-tale signs of SARS-CoV-2 infection is anosmia.
 
For Dr Wesselingh, that’s cause for another concern. If a patient has lost their sense of smell or taste, it’s a sign the virus has got into the olfactory bulb – with the potential to infect nerves or even the brain.
 
‘The olfactory bulb is a common route for viruses to enter the brain. In animal models for SARS, the virus did get into the brain,’ he said.
 
‘We’re now seeing people who have encephalitis while infected with this virus. That raises the concern that there might be a direct viral invasion of the brain, but we don’t know yet. To prove it, you’d have to have samples of brain tissue to see if there are viral particles there.’
 
If the virus can invade the brain, that poses longer term issues for the patient.
 
‘Neurons don’t grow back that well. People with viral encephalitis will often have long-term problems due to that,’ he said.
 
#3: Immune mediated issues
In some patients, a huge immune response to the virus – the ‘cytokine storm’ – between day seven and 10 can be particularly dangerous.
 
‘The virus does induce an inflammatory reaction from the immune system. In the lungs, there tends to be infiltration of lots of immune cells with lots of swelling and fluid,’ Dr Wesselingh said.
 
Perversely, that immune reaction can itself be the cause of death, as lungs fill up with fluid.

Dr Wesselingh said the immune overreaction could lead to other issues.
 
‘Encephalitis could be from the immune overreaction, or from direct viral invasion,’ he said.
 
The impact of the virus on the immune system has led to cases of auto-immune conditions, with Italian hospitals finding five cases of Guillain-Barré syndrome associated with COVID-19 among an estimated 1000–1200 patients, according to a letter to the New England Journal of Medicine sent by Dr Sabrina Ravaglia and colleagues.
 
Dr Ravaglia told MedPage Today that the number represented a ‘strong association’.
 
‘In our series, the neurological complication occurred through a post-infectious, likely immune-mediated, mechanism: COVID-19 symptoms preceded the neurological syndrome, and we failed to find viral RNA in the cerebrospinal fluid of these patients,’ she said.
 
Dr Wesselingh said that Guillain-Barré could be caused by many viral or bacterial infections, but that the Italian cases of Guillain-Barré occurred earlier than he would have expected than for other infections.
 
‘Once the immune system attacks the body, it’s hard to put it back in the box. It can be a long-term problem,’ he said.
 
Auto-immune conditions can be treated with drugs such as tocilizumab, an immune suppressing drug able to dampen immune responses.
 
The drug is being tested in a number of clinical trials to see if it can help patients get through dangerous cytokine storms, while some doctors recommended using approved therapies to tackle hyperinflammation in a letter to The Lancet.
 
After the acute infection phase is over, chronic neurological conditions could emerge, Dr Wesselingh said.
 
‘If you get inflammation of the brain and nerves, it can cause the immune system to continue to target those things incorrectly,’ he said. ‘That means you can have chronic rather than acute auto-immune conditions.’
 
He said it is also possible patients could have residual damage from the acute issue, especially if the virus is reaching the brain.
 
‘Many neuropsychiatrists have concerns over whether this will have an effect on frontal lobe function such as abstract thought,’ he said. ‘[But] that hasn’t been brought out in the literature as yet.’
 
Dr Wesselingh added that even though neurological issues will only affect a minority of people who contract the virus, it is still a concern. Another key issue is the fact that not many coronavirus patients are getting CT scans.
 
‘Given the inability of the nervous system to repair itself well, we do worry because these conditions can affect people for a long time,’ he said.
 
‘We’ve assumed that their altered mental state is because they can’t breathe properly. But we do need to pick up these neurological issues.’
 
He called on doctors in hospitals and the community to involve neurologists if a coronavirus-related neurological issue is suspected.
 
‘Because of the focus on respiratory issues for coronavirus patients, these other issues can be neglected,’ he said. ‘Respiratory issues are not the only thing this virus can cause.’
 
The RACGP has more information on coronavirus available on its website.
 
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“auto-immune conditions” coronavirus COVID-19 neurology stroke