Could Paxlovid treat Covid for a long time? 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 currently being studied as a potential treatment for those who have remained ill months or even years after infection.

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

There is no proven treatment for long Covid.

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

Could this same mechanism operate long after symptoms appear?

No one knows exactly what causes the range of lingering problems associated with long Covid. One of the main theories is that the body could harbor remnants of problematic viruses.

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

“It is known that Covid can reach multiple sites in the body,” she said. “The question is, does it settle there? And is it quiet enough that our immune system doesn’t get rid of it adequately?”

The researchers hypothesize that Paxlovid might be able to have a measurable impact on this remaining virus, if that is indeed what is causing the long Covid.

The Stanford study aims to recruit 200 adults who have had long Covid symptoms for at least three months, with no recent diagnosis of the disease.

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

The results are expected within the next year.

There is already evidence that people who take Paxlovid for Covid are less likely to develop lasting symptoms. A Department of Veterans Affairs study published earlier this month found that people who received the antiviral right after their Covid diagnosis were 26% less likely than patients who did not take the drug to have persistent symptoms three months later.

The findings of the VA study may not apply to everyone. All participants were at least 60 years old or had other health conditions that would increase their risk of complications.

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

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

The Al-Aly team also plans to study Merck’s Covid antiviral, molnupiravir. This medicine is allowed for use in the first days of an infection, but only in patients who for some reason cannot take Paxlovid.

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

Some heal after weeks or months.

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

“If they get sick with Covid again, they can start over or even get worse,” she said.

Verduzco-Gutierrez said studying Paxlovid in people who have had Covid for a long time “makes sense” because “sometimes viruses hide in certain cells, and it’s hard to get to them.”

Will the drug succeed in killing any remaining virus?

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

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

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

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

Fimbres tried naltrexone, a drug that usually treats addiction, to alleviate his brain fog without success. Otherwise, he says, his doctors have nothing else to offer.

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

“I just go on hope.”

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