Could Paxlovid cure long Covid? A major new study aims to find out

Paxlovid – the only drug people can take at home to treat an active case of Covid – is now being studied as a potential treatment for those who have remained ill months or even years after becoming infected.

“There are people out there who are still hurting,” said Dr. Linda Geng, co-director of the Stanford Post-Acute Covid-19 Syndrome Clinic in California. “We need to find effective therapies.”

There are no proven treatments for long Covid.

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Geng and his colleagues at Stanford Medicine have embarked on the first clinical study to test whether Pfizer’s Paxlovid can help relieve symptoms of fatigue, weakness or brain fog. The antiviral has already been shown to be effective in protecting against serious illness when used within five days of becoming ill. It prevents the virus from replicating inside the body.

Could the same mechanism work long after the onset of symptoms?

No one knows exactly what causes the array of lingering problems associated with long Covid. One leading theory is that the body may harbor problematic fragments of remaining viruses.

“There are clues that are piling up,” Geng said, pointing to research that has detected the virus in the intestines, as well as in stool and blood samples months after the initial infection.

“Covid is known to go to multiple sites in the body,” he said. “The question is, does he set up shop there? And is he quiet enough that our immune systems don’t get rid of him properly?”

The researchers speculate that Paxlovid may be able to have a measurable impact on that residual virus, if that is indeed what causes long-term Covid.

The Stanford study aims to enroll 200 adults who have had long-lasting symptoms of Covid for at least three months, without a recent diagnosis of the disease.

Half of them will receive the actual drug, while the rest will receive a placebo. While Paxlovid is typically given for five days, this study has participants take it for 15. This is intended, in part, to address the possibility that the drug may need more time to work well. Many newly diagnosed Covid patients have reported rebound symptoms after their typical five-day course of treatment.

The results are expected next year.

There is already evidence that people who take Paxlovid for Covid are less likely to develop long-lasting symptoms. A Department of Veterans Affairs study released earlier this month found that people who took the antiviral soon after being diagnosed with Covid were 26% less likely than patients who didn’t take the drug to have ongoing symptoms three months later.

The results of the VA study may not apply to everyone. All participants were 60 or older or had other health problems that would increase their risk of complications.

Dr. Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis, led the study. The principal Covid researcher said that while he is eager to see how Paxlovid fares in the Stanford study, he suspects the drug may not be helpful after someone has already been in pain for a while.

“We really feel that with the long Covid, you shouldn’t wait until you already have all these problems to deal with them. We think it’s too late,” he said. “You want to nip it in the bud.”

Al-Aly’s team also plans to study Merck’s Covid antiviral, molnupiravir. That drug is licensed for use in the early days of an infection, but only in patients who cannot take Paxlovid for any reason.

The American Academy of Physical Medicine and Rehabilitation estimates that 29 million Americans have long had Covid.

Some heal after weeks or a few months.

Others get worse, especially if they get reinfected, said Dr. Monica Verduzco-Gutierrez, chair of the department of rehabilitation medicine at the Long School of Medicine at UT Health San Antonio. She is not involved in either the Stanford research or the VA research.

“If they get Covid again, they can start from square one or even get worse,” he said.

Verduzco-Gutierrez said studying Paxlovid in people with long-term Covid “makes sense” because “sometimes viruses hide in certain cells and it’s difficult to reach them.”

Will the drug succeed in killing any remaining viruses?

“I don’t know,” he said. “We will see.”

Bill Fimbres was Stanford’s first participant in the Paxlovid trial. (Courtesy of Stanford Medicine)

Bill Fimbres, 67, of Mountain View, California, was Stanford’s first participant in the Paxlovid trial, receiving his first dose on Monday. (He won’t know if he received the real drug or a placebo until the study is complete.)

He has been struggling with the effects of the long Covid for a year and a half. He still can’t smell or taste it. He has extreme tiredness, balance problems and difficulty “thinking clearly,” he said. “It’s like you have someone else’s brain.”

Fimbres has tried naltrexone, a drug he usually treats addiction, to relieve his brain fog without success. Otherwise, she said, his doctors had nothing else to offer.

“If I could get rid of just one of my symptoms, that would be great,” she said.

“I’m just hoping.”

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