Long COVID may be due to the virus sticking around after infection, researchers say

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LEILA FADEL, HOST:

What's behind long COVID? That's the question frustrated patients and scientists have been working to answer for several years, and now it seems one possible explanation for the condition is gaining traction. NPR's Will Stone has more on those looking to solve long COVID's mystery.

WILL STONE, BYLINE: Brent Palmer's research on long COVID started before that phrase meant anything. Palmer had some friends who'd caught the virus while on a ski trip. It was March 2020. And they'd returned home with this new illness. Palmer works at the University of Colorado, where he studies how the immune system responds to infectious diseases. So this was too good to pass up. He started collecting their blood and was intrigued by one person in particular.

BRENT PALMER: I was up there maybe a month and a half after they had SARS-CoV-2, and she was still complaining of heart palpitations, chest pains, some difficulty breathing.

STONE: Palmer was analyzing part of the immune system's arsenal known as T cells, and, he noticed, unlike the others, her blood still had a very high percentage of these immune cells aimed at the virus.

PALMER: So I just kind of shelved that and thought, well, that's interesting.

STONE: He says, typically, T cells reach very high levels during the acute infection, and over time, they drop off. So he was surprised as he began looking at the T cells of more and more long COVID patients well after they had been infected.

PALMER: These individuals had frequencies that were 100-fold higher in some cases than the individuals that didn't have any sort of persistent symptoms.

STONE: Those with long COVID also had higher levels of systemic inflammation that was associated with worse lung function. It had been months since their infection, but it was like their immune system was still fighting the virus, which raised the question.

PALMER: Even despite the fact they test negative in a nasal swab, the - is the virus still persisting in the lung? Is it persisting in some other organ?

STONE: Many scientists working on long COVID have wondered the same thing over the past few years. Maybe the virus isn't entirely gone. Maybe there are viral reservoirs hiding in the body. And with each new piece of evidence, the case for this is getting stronger. Take the findings of David Walt at Harvard Medical School. His team detected proteins from the coronavirus, mostly the spike protein, in the blood of some long COVID patients up to a year after their infection.

DAVID WALT: And the only place it could be released from is from, you know, some sort of reservoir, some source of virus that continues to spew these proteins out.

STONE: It was a relatively small study, and Walt says as they've looked at more long COVID patients, it appears only about 20% have viral proteins in their blood. But for those who do...

WALT: We think that this is, you know, to some extent, a smoking gun for the presence of, you know, a persistent, active viral infection.

STONE: Then there are all the places in the body where scientists have unearthed evidence of the virus, like in biopsies of the gut or in the stool of people who'd had COVID months earlier. Dr. Dan Chertow at the National Institutes of Health led a painstaking autopsy study of people who'd had COVID.

DAN CHERTOW: We found virus in over 30 different cell types in tissues really throughout the body.

STONE: Essentially, all the major organs, like the lungs, kidneys, liver, heart and throughout the brain.

CHERTOW: It, you know, provides definitive evidence that the virus is capable of spreading to parts all over the body, that it is capable of persisting all over the body.

STONE: In one case, they found genetic material from the virus had persisted for 200 days. And in another...

CHERTOW: In an individual that died relatively early, within two weeks of their initial illness, we were able to culture live virus in the brain.

STONE: He says you can only take so much from this study. After all, it wasn't focused on long COVID, and the people tended to be older and sicker. But Chertow says their findings do provide strong biological plausibility that viral reservoirs may play a role. So where does all of this evidence leave us in the hunt to uncover the roots of long COVID? Microbiologist Amy Proal sums it up this way.

AMY PROAL: No one thinks that every long COVID patient has the exact same thing happening, but we do think that of the research that has come out recently, that reservoir of the virus in tissue ranks at the top of what might be happening to a good number of patients.

STONE: Proal is president of the nonprofit PolyBio Research Foundation, which is working with scientists to advance this theory of viral persistence.

PROAL: Does it persist more in certain body sites over others? If it does persist in one body site, does it have a different mechanism of how it sticks around there? Like, all these nuances of how it's sticking around, we need further research on.

STONE: Mohamed Abdel-Mohsen at The Wistar Institute says scientists now need to draw a clear line from viral reservoirs to the long COVID symptoms. He says it's possible the body's immune response to the virus or parts of the virus is behind some symptoms.

MOHAMED ABDEL-MOHSEN: A chronic reaction to something could lead to immune dysfunction and inflammation. Anything happening in a long period of time can cause our immune system to be, quote, "exhausted and dysfunctional."

STONE: Now, there are many theories about what's contributing to long COVID. For example, Abdel-Mohsen wants to know if viral reservoirs in the gut are responsible for bacteria and fungi leaking into the bloodstream. Scientists are also looking at the role of autoimmunity or damaged tissue or tiny blood clots. The list goes on. Abdel-Mohsen says it's important to realize that some of these theories are not mutually exclusive.

ABDEL-MOHSEN: Each one of them could happen independently and can lead to a problem to our immune system, but it can all lead to each other.

STONE: Figuring out which treatments work for long COVID can also help untangle what's going on here. There's keen interest in using antivirals, like the COVID drug Paxlovid, because it might help extinguish any residual virus. A trial at Stanford expects to have results on that later this year. But some people aren't waiting for that data.

SCOTT LEDUC: I did see some dramatic benefit.

STONE: Scott LeDuc has dealt with long COVID since early in the pandemic. About three months ago, he found a doctor who was willing to prescribe him Paxlovid for 15 days.

LEDUC: All of a sudden, I was able to go for longer walks. You know, I'm starting to push myself a little bit. I was actually starting to introduce some light jogging.

STONE: After struggling for so long, he says it was euphoric.

LEDUC: I truly felt well, that I was almost back to my previous self.

STONE: It didn't entirely last, though. Within a few weeks, LeDuc found himself backsliding. But he says the medication did give him a new, improved baseline, and it also gave him something else - a bit of hope.

Will Stone, NPR News.

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