The Roots of Long COVID in the Brain: Your Health Fast, Episode 3

Lewis: Hello and welcome to Your Health Quickly, a podcast series from Scientific American!

Fishman: On this show, we highlight the latest major health news, discoveries impacting your body and mind.

In each episode we dive into a topic. We discuss diseases, treatments and some controversies.

Lewis: And we’re demystifying medical research in ways you can use to stay healthy.

I’m Tanya Lewis.

Fishman: I’m Josh Fischman.

Lewis. We are Scientific American’s senior health editors.

fishman: Today we are talking about new research on Long COVID. It shows that this mysterious, disabling condition may have its roots in the brain.

Rashid: I think the biggest long COVID challenge I faced was that I had so much pain in my legs that I couldn’t walk. I used a wheelchair and a cane. I used to run races and marathons and now I need a cane to get around.

fishman: This is Ibrahim Rashid. He is 23 years old and from Chicago. I met him at a conference a few weeks ago. (You can hear some of the conference buzz in the background.)

Rashid: I got COVID in November 2020 and my life hasn’t been the same since. In December 2020 I noticed that I was still having trouble breathing. I woke up in the night with severe heart palpitations. And I had trouble breathing, gasping for air.

Lewis: Man, that sounds really badass. He seems to have been through a lot.

fishman: He had a difficult time. And he is one of an estimated 16 million people in the US who have long been ill with COVID, with two to four million left unemployed.

Lewis: In general, a long COVID means you still have symptoms, such as pain or extreme fatigue, months to years after infection. Or something called “brain fog” if you’re having a lot of trouble concentrating or remembering things (more than the normal amount!).

The persistent nature of these symptoms is one of the reasons patients are often referred to as “long-distance drivers.” It was a difficult condition to manage or treat.

fishman: Recently, however, a common thread has emerged in this labyrinth of symptoms: the brain.

Lewis: Hm. The brain makes sense of things like memory problems, but how is physical pain and fatigue related to the brain?

fishman: Fair question. Initially, signs of the virus showed up in the brain and central nervous system. We often think of COVID as an infection that mainly affects the lungs, throat and nose. But it also affects many other organ systems.

A study has found evidence of virus particles in the brains of people with long COVID. Another found viral genetic material in the brain 230 days after infection.

Lewis: Wow. That’s almost…eight months.

fishman: Yes. And it turns out the nose is actually a route for the virus to reach the brain. Viral material has shown up alongside neurons deep in the lining of the nasal passages. Projections from these neurons go up into the brain, to areas that control breathing and the heart.

Also, autopsies of the brains of people who have died from COVID find signs of immune system activation, as if there had been a response to infection.

There are cells called macrophages that go after invading microbes. The problem is that macrophages are not very accurate. When they attack, they produce chemicals that chew up nearby cells. There can be a lot of inflammation and damage.

Lewis: Immune cells also travel through the blood and spinal fluid, and the brain is filled with tiny blood vessels. So a sustained immune response could damage these vessels and neighboring brain cells.

fishman: Exactly. For this reason, William Pittman, a doctor at UCLA Health who works at a long-running COVID clinic, says he now views the condition as both a neurological and respiratory disorder.

Lewis: That is interesting. But how does that explain the wide variety of symptoms people experience?

fishman: Because of a so-called dysautonomia.

Lewis: Hmm, I heard about that. What did you find out about it?

fishman: Well, there are all these activities in your body that the brain normally takes care of automatically, like breathing, blood pressure, heartbeat, and balance by sending signals along nerves throughout the body.

Dysautonomia is when the brain loses this control. Ibrahim described it to me:

Rashid: If I tried to move my leg. It would feel like it was taking longer, like there was a few milliseconds of delay. And I would look at it. I think I’m moving it back and forth. But progress is slower. And then I felt unstable and I thought wait, why am I losing my stability? I can stand and suddenly I can’t anymore.

fishman: This loss of control can also occur in the heart.

For many long-term COVID patients, their hearts start racing when they stand or sit up. It can accelerate by 30 beats per minute!

And that creates fatigue, among other problems. Many people with long COVID just crash when they exert themselves. Ibrahim told me about an episode when he was studying for a big exam – he was a student – and couldn’t get out of bed for ten days afterwards.

Lewis: Oh my God. There are a few ways to handle this, right? Beta blockers, a type of medication that lower heart rate, have been effective in some people.

Fishman: Yes. There is still a lot of uncertainty with long COVID treatments – what works for one person may not work for another – but viewing it as a brain-body disorder can help focus therapy.

Lewis: That’s right. In long COVID patients who may have nervous system inflammation, doctors have tried giving them a cocktail of proteins and antibodies called intravenous immunoglobulin, or IVIg. This dampens the inflammatory immune response.

Fishman: Our colleague Stephani Sutherland wrote about this therapy and several others in a SciAm cover story in the March issue.

She said some long-lived COVID cases could be caused by the virus lingering in the body. You and I talked about the evidence for that.

Lewis: For these people, it may make sense to treat them with antiviral drugs. In fact, there is an ongoing clinical study looking at using Paxlovid to treat long-term COVID.

And a Veterans Affairs study found that taking Paxlovid when infected reduced the risk of developing long-term COVID conditions by 25 percent.

fishman: There is also some evidence that COVID vaccines reduce the risk of long-lasting COVID symptoms. However, it is not clear by how much. A recent study says it halves the risk. But another showed a smaller reduction of about 15 percent.

fishman: But it’s not just about drugs. For people with long COVID, like other diseases that don’t have easy medical answers, the big problem is finding people to believe you.

Doctors, friends and even family all too easily say things like “it’s all in your head”. Ibrahim heard that often.

Rashid: People didn’t understand why young people like me are still struggling. I’ve lost friends who just got fed up with me being sick just six months into my illness.

Lewis: How is he now?

fishman: Better, much better. He was walking without a stick when I saw him. He has adjusted his diet and gets plenty of rest to reduce the risk of ongoing inflammation.

And he co-founded a company called Strong Haulers. They’re developing an app that can pull data from wearables like Fitbits and Apple Watches.

The idea is to give people with chronic conditions information about activities that trigger symptoms and activities that reduce them.

Lewis: That’s cool. This seems to be self-help. And it could provide them with data to share with doctors to validate their symptoms.

fishman: And these symptoms tell the medical community that COVID is a long time coming is not everything in the head. But it does seem to be in the brain.

fishman: Your Health Quickly is produced and edited by Kelso Harper, Tulika Bose and Jeff DelViscio. Our music is composed by Dominic Smith.

Lewis: Our show is part of Scientific American’s Science, Quickly podcast. You can subscribe wherever you get your podcasts.

fishman: And don’t forget to go to for the latest and most in-depth health news.

Lewis: I’m Tanya Lewis.

Fishman: I’m Josh Fischman.

Lewis: We’ll be back in two weeks. Thanks for listening!

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