New research offers clues to what causes long COVID — fuelling hope for eventual treatments

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For several years, scientists have tried to untangle one of COVID-19's persistent puzzles: Why do some people, even after mild infections, go on to develop lasting health issues? And crucially: How do you prevent, treat or even cure those lingering symptoms?

Now, fresh clues are emerging. Several research teams have honed in on potential hallmarks of long COVID, formally known as post-COVID-19 condition, offering insight into the possible mechanisms at play. 

Other researchers, meanwhile, are finding overlaps between long COVID and the persistent symptoms some people experience after other types of infections, from influenza to the common cold — suggesting there may be similar triggers for a wide range of little-understood conditions.

There are no smoking guns yet. Still, emerging research could bring scientists one step closer to figuring out treatments to ward off post-infection symptoms ranging from debilitating exhaustion to life-altering "brain fog."

"We're getting the sense that there are some tangible mechanisms that can produce some of these symptoms," said Christoph Thaiss, an assistant professor of microbiology at the University of Pennsylvania's Perelman School of Medicine. 

"And many of them might actually be, surprisingly, shared among many of these conditions."

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Two recent studies have tried to tease out long COVID biomarkers — traits in someone's blood, tissues or bodily fluids that can be measured and tracked, at times offering signals of an infection or disease. (Blood pressure and high cholesterol, for instance, are both common biomarkers physicians analyze at routine medical appointments.)

One new paper, from Thaiss and others at the University of Pennsylvania, was published on Monday in the journal Cell. It looked at both real-world patients — some with long COVID, others who fully recovered — and animal models.

Their research suggests the release of interferons — a group of signalling proteins that cells send out as an alert system when there's a viral threat — could drive the depletion of a key chemical messenger, serotonin. In turn, that may lead to cognitive impacts such as memory issues or a feeling of "brain fog."

The team was surprised to find that some people with long COVID still had virus fragments lingering in their guts, long after they were no longer testing positive for the virus. Those particles, located through stool samples, might be enough to trigger the release of interferons. 

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That could set off a chain reaction, leading to inflammation that makes it tougher for the digestive system to absorb tryptophan — an essential amino acid found in food that helps the body make serotonin.