Short Wave - What We Know About Long COVID, From Brain Fog to Fatigue

Episode Date: March 13, 2024

"Long COVID has affected every part of my life," said Virginia resident Rachel Beale said at a recent Senate hearing. "I wake up every day feeling tired, nauseous and dizzy. I immediately start planning when I can lay down again." Beale is far from alone. Many of her experiences have been echoed by others dealing with long COVID. It's a constellation of debilitating symptoms that range from brain fog and intense physical fatigue to depression and anxiety. But there's new, promising research that sheds light onto some symptoms. NPR health correspondent Will Stone talks with Short Wave host Regina G. Barber about the state of long COVID research — what we know, what we don't and when we can expect treatments or even cures for it. Have more COVID questions you want us to cover? Email us at [e-mail] — we'd love to hear from you.See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Hey, everyone. It's Regina Barbara here. And I'm with NPR's health correspondent Will Stone. Hey, Will. Hey, Gina. Okay, so about four years ago, scientists at the CDC discovered the first COVID case in the U.S. I do remember this, Will, because I was living in Washington State at the time, and so were you. And you were on the ground covering this story.

That's right. This was pre-vaccine, pre-masked days. It was a very different reality. At the time, we didn't really know a lot about the virus itself, and we'd learn a lot over the next four years. But there's still one big mystery alluding scientists, and that's long COVID. Okay, so long COVID, that's the diagnosis that can happen after somebody's gotten COVID-19, and it can last for months and even years. Exactly. It can really upend people's lives. I was watching a Senate hearing about long COVID, and I was really struck by one person who spoke about it.

Rachel Beale, she lives in Virginia, and she's had long COVID for all. almost three years. I had a very full life before I got sick. Long COVID has affected every part of my life now. I wake up every day feeling tired, nauseous, and dizzy. I immediately start planning when I can lay down again. I mean, I'll tell you, Gina, I've heard different versions of racial's experience echoed by tons of other people with long COVID.

It's this constellation of debilitating symptoms, brain fog, intense physical fatigue, even depression and anxiety. most people have lost months, maybe even years to this illness, and they describe just extreme frustration at not having any answers. There are still no validated treatments for long COVID. There's really no widely established biomarker you can use to diagnose it. Long COVID clinics are hard to get into. There's often a wait list. And even if you do get seen, most scientists don't think this is just one illness. They think it's many different ones. Wow. Okay. So there's so many unknowns with treating it, much less curing it, right?

Definitely, but a lot of scientists are working on this. And there have been a string of promising studies they put out. I've covered a few of them that identify some of the potential underlying drivers of long COVID. Today on the show, Long COVID, what we know, what we don't, and when we can expect treatments or even cures. You're listening to Shortwave from NPR. Okay, well, you said that long COVID is probably not just one illness.

What do you mean by that? Yeah, so more and more, there's a recognition that long COVID is kind of a catch-all. It's a way of describing a collection of different syndromes that emerge in the wake of an infection. Some people have such intense physical fatigue that they're just heaving going up a flight of stairs. There's also debilitating brain fog or difficulty thinking or concentrating, along with headaches, diarrhea and GI problems, sleep problems. I mean, you could have all of these symptoms or you might just have one or two, but for some people, this can be extremely severe.

So are there any trends in these differences? Well, clinicians have noticed the illness seems to play out differently depending on who gets it. So, for example, the brain fog, the fatigue, malaise, this cluster of symptoms, it's more common in younger adults and females. Whereas cardiovascular and metabolic problems tend to crop up more in older folks, especially those with other medical conditions. So does that mean there's also different causes as well? We just don't know yet. Many experts do think that's the case, though. There are a handful of different hypotheses floating around about long COVID.

One that's getting a lot of attention these days is that remnants of the virus, maybe it's genetic material or protein or something, they don't know yet, can stick around in your body and create a kind of chronic infection. And this idea is sometimes called viral persistence. Wow. So are there any, like, other ideas? Yes. It's possible that the infection just sparks problems with the immune system, creates dysfunction.

Maybe that leads to autoimmunity where the body essentially attacks itself. There's also intense interest in the role of the gut microbiome, also inflammation in the vascular system, problems with the mitochondria. The tricky thing here, Gina, right now, is that scientists are finding all of these biological abnormalities, but they're not quite sure what is at the root of the illness. And to make things even more complicated, it's possible multiple things are happening in some patients, but not others. Okay. So with those basics out of the way, let's get into some of the specific research into long COVID. Like, first up, research into the physical fatigue many people experience. Like, what do you know about that? So this is formerly called post-exertional malaise, and it's a hallmark of long COVID and other complex illnesses. This is essentially the escalation of symptoms after someone exerts themselves.

It is very clear that this is not a typical response to exercise. That's David Petrino. He's the director of rehabilitation innovation for Mount Sinai Health System. He says that if people with post-exertial malaise who try to hit the gym or even do what would have been a light amount of physical activity, like chores around the house, they tend to crash. They feel incredibly unwell. They become bed-balanced. Their whole system feels as though they've been poisoned. So David runs a long COVID clinic at Mount Sinai.

And he says this idea that exercise can be able to be able to be able to be able to be able to be able to be able to be able to. can help patients, that they're just deconditioned. It's been hard to shake, even though there's evidence suggesting that this is definitely not the case, there's more going on with these patients than just simple deconditioning. Yeah, no, it totally sounds like it's making it worse. It is, that's right. And actually a study published last month in Nature Communications found exactly this. Basically, researchers compared 25 people with long COVID to those who had had COVID and

fully recovered. So they put both groups on stationary bikes and gave them a 10 to 15 minute. exercise test. Then they drew blood and they took muscle biopsies from their legs before and after the exercise. What we saw immediately, and it's very profound, is that their mitochondria don't function in a healthy way. That's Braden Charlton. He's a physiologist at Vryi University in Amsterdam. He's one of the studies authors. And he says the mitochondria in the group with long COVID were obviously compromised. The tissues were basically starved for energy. And And there were, quote, immense amounts of cell death, which happens when immune cells infiltrate and degrade the tissue.

And that wasn't the only thing they found. There is a lot more muscle breakdown than we would expect to happen following the exercise. Braidenstein found this had nothing to do with how people's lungs or hearts are functioning, which, you know, you might expect with aerobic exercise. There's something else making it hard for their muscles to take up that oxygen in their blood. This really sounds scary, honestly. But are there any leads of what's causing this post-exertional malaise? So one thing the researchers found in the patient's muscles were these tiny blood clots. These blood clots indicate that the lining of the blood vessels is basically inflamed and compromised.

And that can impair the delivery of oxygen. So in the long COVID group, more clots happened after exercise, which reinforces that this isn't something you can fix by telling people to work out more. You can actually make it worse. Okay. So let's talk about another really stubborn sim. I hear about, and that's brain fog. Like, what's going on with that? Yeah, so brain fog probably has a few different causes.

Researchers have found evidence of a leaky blood-brain barrier in people with brain fog. Oh, my gosh. Yeah, I mean, there's a lot of interest also in neuroinflammation and the role of the immune system in the brain. It's not clear what exact mechanism is leading to these neurological symptoms, but there is a promising study done in mice that might help explain some of it. Okay, so this is early stages. Just tell me more about this. So the researchers first picked up on a clue when they looked at the blood of long COVID patients.

And they noticed that there was a lack of serotonin circulating in the body following a COVID infection. That research was published in the journal Cell in October of last year. Okay. So with serotonin on their minds in this discovery, the researchers tried to start from the very beginning of the disease process. They used experiments on mice to trace its course. And the team, which is at the University of Pennsylvania, they thought that this lack of serotonin, might have something to do with viral persistence, which I mentioned earlier, also called a viral reservoir, and that's the idea that there's a lingering infection in a specific part of the body.

What is interesting is that 90% of the serotonin in the body is actually made in the gut. So that's Maya N. Levy. She's a microbiologist and a senior author on this latest paper. She says they looked for evidence of this viral persistence by checking the stool of long COVID patients for genetic material from the virus. About 30% of the patients, we could find viral RNA in their gastrointestinal tract. Okay, so you're telling me that serotonin is mostly produced in the gut, and that's why a gut viral reservoir might be screwing with these hormones and causing brain fog. Well, yeah, maybe. Okay, okay.

Levy says that when you have this inflammatory response in the gut, which is what they saw, that can deplete supplies of serotonin in the body. And they notice this in mice and then followed that pathway, from the gut to the vagus nerve. And this is kind of like a monitoring system of the body. It links the brain to the gastrointestinal tract and other organs. But how does this all affect the brain? Yeah.

So without that serotonin or without as much of it, the communication between the brain and the vagus nerve is impaired. And that then reduces activity in a region of the brain called the hippocampus. And they think that could be what people experience as brain fog. So is this something that can be reversed? Well, the researchers are hopeful. Christov Tice, another senior author on the paper, told me they were able to reverse brain fog in mice. We can make the animals remember perfectly again by just reactivating their vagus nerve or by restoring their serotonin signaling. In this experiment, Gina, they gave the mice a generic form of Prozac.

That's a medication known as an SSRI, and it's typically prescribed for depression, and it works by increasing the serotonin circulating in the brain. So that's one area that needs to be looked at in a crossactivity. clinical trial to see if it really works in humans. And we have to remember, of course, that this was done in mice, not in humans. Right. So please don't rush home and take Prozac. But this sounds like a hopeful avenue of research, right? Yeah, this paper got an enormous amount of attention when it came out. You know, these are just two studies that only explain two symptoms of long COVID. And scientists say a patient may ultimately need multiple different treatments to deal with all their symptoms. I mean, that's really tough to hear, especially for people who have like self-managed this,

really life-changing thing for multiple years. It's definitely unsettling, and many doctors feel like they're still trying to get a handle on this. They feel unmoored because they just don't know how to help their patients yet. That's what I heard from one doctor named Resika Karnik. She's the medical director of UChicago Medicine's post-COVID clinic. You know, you do sort of feel like you're out in the wilderness, but it's hard to look a patient in the eye and say we're not quite sure yet and to keep repeating that. Yeah, it sounds like this is something that's going to take like a big push to really

solve from doctors, researchers, but also from the government funding it, right? That's right. There is a growing network of scientists who are working on this problem. Many are actually now relying on private funding from philanthropists to push this research forward. Congress has allocated more than a billion dollars for long COVID research. And there's been some new funding announced by the NIH recently, but patient advocates have told me repeatedly that a problem of this scale just doesn't get solved with. without billions of dollars, and that's billions, plural. Mm. Okay, well, I mean, I guess let's hope that if long COVID's getting more attention, maybe you'll get more funding soon.

Thank you so much for bringing us the latest on long COVID research and a look at the road ahead. Happy to do it, Gina. You can find more of Willstone's long COVID reporting at npr.org. Before we head out, a quick shout out to our shortwave plus listeners. We appreciate you and we thank you for. being a subscriber. Shortwave Plus helps support our show. And if you're a regular listener, we'd love for you to join so you can enjoy the show without sponsor interruptions. Find out more at plus.npr.npr.org slash shortwave. This episode was produced by Margaret Serino,

edited and fact-checked by Britt Hansen. Our showrunner is Rebecca Ramirez. The audio engineer was David Greenberg. I'm Will Stone. I'm Regina Barber. Thank you for listening to Shortwave from NPR.