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Scientists are beginning to understand how long COVID symptoms affect the brain

ARI SHAPIRO, HOST:

Months or even years after getting COVID-19, some people still have neurological symptoms like pain, fatigue and brain fog.

MICHELLE WILSON: It started to occur to me that this could be permanent. This might be as good as it gets.

SHAPIRO: NPR's Jon Hamilton reports on what scientists are learning about how long COVID affects the brain and nervous system.

JON HAMILTON, BYLINE: When the pandemic struck the U.S. in 2020, thousands of nurses got sick. Michelle Wilson was at Barnes-Jewish Hospital in St. Louis.

WILSON: I worked in the PACU, which is the pre- and post-surgery. I got people ready for surgery and woke them up after their surgeries, and I loved that job. It was great.

HAMILTON: Wilson got COVID in November. When it got bad, she went to the emergency department at her own hospital.

WILSON: I had bilateral pneumonia, and I was in sepsis by that time. My blood pressure was really low, and I had irregular heartbeat, and I got admitted upstairs for a couple days.

HAMILTON: The infection was affecting her lungs and also her brain, including circuits that control blood pressure and heart rhythm. Today, three years later, Wilson still isn't back at her nursing job. One reason - her memory.

WILSON: You know what? I forgot your question. I forgot where I was going.

HAMILTON: Oh.

WILSON: And this happens. I have trouble with word retrieval, concept retrieval and sometimes, like, remembering where I was going.

HAMILTON: So do other long-haulers. Long COVID affects millions of people in the U.S., and many, if not most, have neurological symptoms. Scientists say one reason is that COVID seems to weaken the barrier that usually separates the body and brain. Dr. Ziyad Al-Aly sees lots of long COVID patients in his work at Washington University School of Medicine and the VA health care system, both in St. Louis.

ZIYAD AL-ALY: Recovery is rare, and when you talk deeply to patients, they've actually adjusted to a new baseline. They used to walk the dog, you know, two blocks, and now they do only half a block. They used to go to a couple dinners a week with friends. Now they only do once a month.

HAMILTON: Early in the pandemic, doctors saw what COVID could do to internal organs. But Al-Aly says it soon became clear that the damage doesn't stop there.

AL-ALY: Unfortunately, long COVID as we know it now - it can affect nearly every organ system, including the brain.

HAMILTON: When that happens, patients report a wide range of symptoms. Al-Aly says about 40% have trouble sleeping at night or staying awake during the day.

AL-ALY: People experience sleep disturbances. As a result, they wake up fatigued. Even minimal exertion, you know, puts them into a state of, you know, profound fatigue.

HAMILTON: And poor sleep, he says, can also contribute to pain.

AL-ALY: Pain is a big deal. And it's not really only, oh, my wrist is hurting, or, my knee is hurting. It's really almost like the whole body aches.

HAMILTON: Michelle Wilson, the nurse, says when she first came home from the hospital, she was in agony.

WILSON: The pain across my chest and in my arms was so bad that I slept on this couch like this, with pillows under both arms, because I couldn't stand my arms to touch my chest.

HAMILTON: Now Wilson is able to do things like make breakfast or take a shower, but she still hurts, which could signal ongoing inflammation or damage to nerve cells that sense pain. Wilson's doctors aren't sure. That's because scientists are just beginning to understand what COVID does to the brain and nervous system. Dr. Troy Torgerson is at the Allen Institute for Immunology in Seattle.

TROY TORGERSON: There's still a ton, we don't know. So I would say we're still a little ways away, but we're nibbling away at it bit by bit.

HAMILTON: Torgerson and a team of researchers studied 55 people who had symptoms at least 60 days after a COVID infection. The team analyzed blood samples, looking for proteins that signal inflammation somewhere in the body.

TORGERSON: We saw persistent, ongoing immune activation in about half of the long COVID patients that we studied.

HAMILTON: Torgerson says it's not always clear what's causing the immune system to respond, but once it does, it can affect the brain even if the virus itself doesn't infect brain cells. For example, immune cells or antibodies from the body may cross into the brain and damage neurons, or the infection may activate a special set of immune cells in the brain itself. Torgerson says the symptoms of long COVID can resemble those of autoimmune diseases, which occur when the immune system mistakenly attacks healthy cells.

TORGERSON: We certainly see brain fog in other diseases. So, for instance, in lupus, it's one of the signs of neurological lupus.

HAMILTON: Fatigue is another common symptom in autoimmune disease and something Michelle Wilson deals with every day.

WILSON: Sometimes I am less able to do something than my 87-year-old mother. She is the one who's, like, always telling me to sit down, and she's running up the stairs for me so that I don't have to do it. And that feels terrible.

HAMILTON: To understand how long COVID affects a human brain, scientists have been studying mice. Dr. Robyn Klein of Washington University in St. Louis has been working with mice to develop a mild version of the disease.

ROBYN KLEIN: And those animals do have cognitive deficits a month after they were infected. They no longer have virus. They're no longer ill. But they can't remember and recognize things.

HAMILTON: Klein says in these animals, the infection appears to weaken the blood-brain barrier, allowing the body's immune response to affect brain cells. She says the result is inflammation that causes subtle but significant changes in the brain.

KLEIN: There's not a lot of dead cells. It's not like there's a multitude of dying neurons. What there is is there's elimination of the connections between neurons.

HAMILTON: In other words, synapses, the brain's wiring, which is critical to memory and thinking. Klein suspects that inflammation is causing a similar kind of damage in the brains of people who get long COVID. And she says this can occur even in people who don't get very sick.

KLEIN: You and I may handle different viruses differently, and I may end up getting more inflammation in my brain than you because we have a different genetic makeup.

HAMILTON: Klein says one way to protect the brain during an infection may be drugs that reduce inflammation, and studies to test that idea are already underway. In the meantime, she says, vaccination offers a way for people to reduce their risk of long COVID. People like Michelle Wilson, though, are hoping for treatments that will repair their ailing brains. Before getting COVID, the only medication Wilson took was for a thyroid condition. Now she relies on a daily cocktail of prescription drugs to control conditions like nerve pain.

WILSON: I'm on three medicines for that. And then it also gave me high blood pressure and tachycardia, so I'm on some cardiac meds for that.

HAMILTON: When I asked Wilson which drugs, she pushes herself out of her chair to fetch her pill organizers.

WILSON: So this is...

HAMILTON: So you are showing me not one but two...

WILSON: But two.

HAMILTON: ...Different boxes of...

WILSON: Yeah.

HAMILTON: ...Meds.

WILSON: Morning, noon, night and bedtime. And that's what I take on a day.

HAMILTON: Until researchers come up with something better. Jon Hamilton, NPR News.

(SOUNDBITE OF BUN B AND STATIK SELEKTAH SONG, "STILL TRILL (FEAT. METHOD MAN AND GRAFH)") Transcript provided by NPR, Copyright NPR.

NPR transcripts are created on a rush deadline by an NPR contractor. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.

Jon Hamilton is a correspondent for NPR's Science Desk. Currently he focuses on neuroscience and health risks.
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