How COVID-19 affects the brain

A neuropathologist explains the stranger symptoms of long covid - from mood swings to fizzing in the skin...
11 August 2020

Interview with 

Kieren Allinson, University of Cambridge


A X-ray image of figure clutching their head, with their brain glowing in red.


Barbara Melville asked us to provide some clarity on the neurological side of this disease. Phil Sansom asked University of Cambridge neuropathologist Kieren Allinson...

Kieren - Well I think it definitely can affect the brain, and I think it can potentially do that by a variety of different mechanisms. Potentially the coronavirus could actually infect the brain tissue itself and cause inflammation; what we might call encephalitis in the brain tissue. It might be that the immune system causes excessive inflammation generally throughout the body, including the brain; and maybe the virus doesn't actually enter the brain itself, but it sets up an immune response that causes inflammation in the brain.

Phil - Now it's quite hard, isn't it, for viruses and other stuff to get into your brain, because obviously that's something that the body desperately doesn't want. If that's actually what was going on, how would that be happening?

Kieren - I think there's a variety of possible routes into the brain that viruses do take; for example, the olfactory nerve is where the herpes virus, herpes simplex virus, infects the brain via. It may cross from the blood; so a virus in the bloodstream can cross across the blood-brain barrier, which is the tightest barrier in the human body, it's a barrier that deliberately doesn't let much across, only selectively lets certain things across. It might be the virus can get into the nerves - the nerves that come off the spinal cord, that come off the brainstem - travel backwards in the nerves, and get into the brain that way.

Phil - Do you have any evidence either way? I mean, you're a neuropathologist; what have you seen?

Kieren - I've examined the brains from a few people who had severe COVID-19, and I've seen a variety of different changes. I've certainly seen what we call encephalitis, which is inflammation of the brain - that's white blood cells and other immune cells in the brain tissue, causing inflammation and damage - but I didn't actually detect the virus in the brain tissue. So I don't know whether the virus was there and it sets up this inflammation, or whether the virus was never there, but it sets up the inflammation in the body, and that can cause damage to the brain without the virus ever being directly within the brain tissue. There's no good evidence yet that the COVID-19 virus can directly infect neurons and other brain cells, but it's certainly is possible. The other way I've seen the virus affect the brain is by causing strokes: it might damage the cells that line blood vessels - and the brain's obviously full of blood vessels, little tiny blood vessels - and it can cause them to clot off and form strokes, or little bits of brain tissue that die. And that might be related to the fact that the virus causes this hypercoagulation, it makes your blood more sticky and more liable to clot. So I've certainly seen both forms of brain damage in COVID-19 patients.

Phil - If you had to put money down on anything, what would be your bet? Because people like Paul have talked about... he actually asked us to ask someone like you, he says, "I've had things like wild swings in mood. Sometimes I wake in tears, feel absolutely sad; by the afternoon I'm elated, almost high, ready to conquer the world. No history of mental illness. If you had to put a bet down, what do you think is going on? Is the virus getting into his brain, or what?

Kieren - Well it's been increasingly recognised that it definitely does affect the brain and causes some brain symptoms, neurological symptoms; and something called encephalopathy, where the brain just isn't generally isn't working very well. I think that when they've tested the CSF from patients with neurological symptoms...

Phil - And Kieren - what's CSF?

Kieren - The cerebrospinal fluid, it bathes the brain and spinal cord, and provides it with nutrients, et cetera. And we can test that for the virus. And on patients where they've done that, there hasn't been very many where they've actually detected the nucleic acid of the virus in the cerebrospinal fluid. My guess is more that it's a, what we call a para-infectious process; so it's due to the infection, but not directly due to the presence of the virus. So I think the virus causes this cytokine storm, which is this massive overreaction of our immune system, in susceptible people. And that can damage blood vessels throughout the body. That can cause the blood-brain barrier to become more leaky, so inflammation that normally wouldn't get into the brain - white blood cells that would normally not pass into the brain - might be able to get across this leakier blood-brain barrier.

Phil - Interesting. That's maybe the brain itself; in terms of other neurological stuff, Paul and lots of other people that I've spoken to talk about this fizzing feeling? Paul says it's in his arms and legs; other people say it's in their skin at all times; some call it buzzing, some call it 'peppercorn feeling'. What do you think might be going on there?

Kieren - One of the surprising things that has come out about COVID-19 is it can damage the peripheral nervous system, which is all the tiny little nerves throughout your skin that provide your sensation. This has emerged as a real feature post-COVID, of damage to peripheral nerves causing changes in the sensation of the skin. So maybe loss of feeling, what we call anaesthesia; but also just changes in feeling, unusual or maybe painful feelings just from light touch, et cetera.


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