An extended course of the antiviral drug Paxlovid won’t ease a person’s long COVID symptoms, a new study finds.

People who took Paxlovid for 15 days — three times as long as it’s prescribed for an initial COVID infection — had no better improvement in their long COVID than people taking a placebo, researchers reported June 7 in the journal JAMA Internal Medicine.

“While there are now improved therapies and treatment practices for acute COVID, there’s nothing FDA-approved for long COVID,” said senior researcher Dr. Upinder Singh, chief of infectious disease and geographic medicine at the Stanford University School of Medicine. “People continue to suffer and the numbers keep piling up.”

An estimated 10% to 20% of COVID patients -- tens of millions in the United States alone -- develop long COVID, a collection of symptoms that tend to crop up three months or more after a person’s initial infection.

One theory has held that long COVID might occur due to leftover virus or viral debris that remains in a person’s deep tissues even after they’ve cleared the infection.

“Some studies suggest that viral particles and molecular debris could be responsible for some long-COVID sufferers’ ongoing symptoms,” Singh said in a Stanford news release. “We figured if that’s the case, maybe treating them with Paxlovid could relieve some of these symptoms.”

Between November 2022 and September 2023, the researchers recruited 155 Long COVID patients who’d been infected with COVID more than 16 months earlier. Each participant reported at least two out of six common long COVID symptoms — fatigue, brain fog, shortness of breath, body aches and heart or GI symptoms.

Half the patients were randomly assigned to a 15-day course of Paxlovid, and the rest a placebo. People take five days of the antiviral to fight off an acute COVID infection.

At 10 weeks, there was no statistically significant difference in symptoms between the two groups, researchers report.

The trial did have one positive result, however — it showed that people can safely take a long course of Paxlovid.

“One reasonable implication of our results is that Paxlovid can be given safely for a longer period of time,” Singh said, “for example, in instances where a newly infected patient is immunocompromised.”

Singh said these results, while discouraging, don’t completely rule out the potential for Paxlovid to be helpful in treating Long COVID. For example, future tests might try the drug on people who’ve more recently developed Long COVID.

“Should we have tested patients with symptoms present after only seven or eight months instead of 16 or 17?” Singh said. “Should we have treated them for a longer time? Were we even testing the right patients? Maybe only some symptoms will be responsive to antiviral treatment.”

The team will continue to analyze the results from this trial, to see whether particular people were helped more than others.

The trial was funded by Pfizer Inc., the maker of Paxlovid.