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Coronavirus

Researchers at CU-Anschutz are trying to crack the code on long COVID by looking at T cells

A study suggests using an antiviral drug like Paxlovid may help those with lingering COVID symptoms

A scanning electron micrograph, artificially colored blue, of a health human T cell. (National Institute of Allergy and Infectious Diseases via Flickr)
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Researchers in Colorado have made a key discovery that could help doctors in fighting one of the most pernicious ongoing impacts of the pandemic.

Long COVID-19 — the catchall diagnosis for long-term COVID symptoms that can afflict as many as 30% of people after they have recovered from their initial infection — is so common that it may be a new mass health event. But scientists have struggled to identify what causes the condition, also called PASC for post-acute sequelae of COVID-19.

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Researchers at the University of Colorado Anschutz Medical Campus hope they have begun to crack the code, though, after a study focusing on T cells, the special ops forces of the immune system.

“I’ve been excited about it,” said Brent Palmer, an associate professor of allergy and clinical immunology in the University of Colorado School of Medicine and the senior author of the paper. “I think it’s a pretty important study.”

The study looked specifically at long COVID-related lung problems, which Palmer said is the most common way that long COVID manifests. Researchers recruited 40 participants, half with long COVID symptoms persisting at least four weeks after their initial infection, and half without long COVID.

The researchers found that people suffering from long COVID had virus-specific T cell levels 100 times higher than those who do not have long COVID. The higher T cell levels correlated with higher levels of inflammation.

The study, which was peer-reviewed, was published this spring in PLOS Pathogens.

What makes the research so exciting to Palmer is that it suggests an answer to the long COVID puzzle.

T cells are potent killing machines, quickly identifying infected cells and squashing them. If people with long COVID have high levels of T cells, that could mean they have a lot of coronavirus-infected cells still somewhere in their body, even though they are no longer testing positive for infection. In this explanation, the T cells would attack those hidden reservoirs of virus, also causing damage to the organs that harbor them.

Though best known for its respiratory damage, the virus that causes COVID can spread widely throughout the body. And Palmer said it’s not uncommon with other viruses to find them hiding in the body’s back alleys long after the acute infection is cleared.

“It makes sense that these people with PASC may have low levels of virus in places we can’t measure,” he said.

This explanation also suggests a possible solution: Treat long COVID patients with antiviral drugs like Paxlovid that are designed to block viral replication in the body. Palmer said several studies are ongoing to test just that, after a small case study this spring found that Paxlovid may help long COVID patients.

“The Paxlovid studies will be really informative,” he said.

If the drug doesn’t help with long COVID, then the answer may lie elsewhere. Palmer said it’s possible the high levels of T cells that his team observed could be related not to actively infected cells but to broken fragments of virus floating around in the body and keeping the T cells in attack mode.

It’s also possible that the T cells are a “cross-reactive immune response,” meaning that they have essentially gone rogue and are targeting something in the body that looks like the coronavirus but isn’t. If that’s the case, Palmer said it could be possible to use steroids or other drugs to tame the overactive immune response.

An entrance to the Anschutz Medical Campus in Aurora, photographed on Oct. 18, 2019. The campus houses the University of Colorado Hospital, Children’s Hospital Colorado and the state’s Veterans Affairs hospital, as well as the University of Colorado School of Medicine. (John Ingold, The Colorado Sun)

CU-Anschutz researchers are continuing to dig into the mystery. Palmer has applied for a federal grant to collect lung cells from patients with long COVID — via a procedure called a bronchoscopy. He and his team will then test the cells to see if they are infected with coronavirus, helping to clarify whether a hidden cache of virus is causing the patients’ long COVID-related lung problems.

Ultimately, Palmer said this is an important puzzle for scientists to solve quickly. The Brookings Institution estimated earlier this year that as many as 31 million Americans may have experienced long COVID symptoms, at least temporarily, while more than a million Americans may be unable to work due to long COVID. With continued waves of infection, the problem could get even worse.

“I think this is going to be a serious health concern for many years to come, unfortunately,” Palmer said.


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