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Is antiviral Paxlovid related to COVID-19 rebound?

Experts say a small share of cases ‘rebound,’ meaning the person has COVID-19 again after testing negative

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Zoë Petersen, Deseret News

President Joe Biden and his chief COVID-19 adviser, Dr. Anthony Fauci, both rode out their own COVID-19 infections with light symptoms, courtesy of an antiviral prescription called Paxlovid. And a few days after testing negative, they each had COVID-19 again.

According to a late-May Centers for Disease Control and Prevention health advisory, some people have what’s being called “COVID-19 rebound.” That’s a recurrence of symptoms or a positive COVID-19 test after apparently recovering and testing negative.

What causes a rebound, how often it occurs and whether there are specific factors that make a rebound more likely isn’t clear. The CDC notes that “a brief return of symptoms may be part of the natural history of SARS-CoV-2 (the virus that causes COVID-19) infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”

Despite incomplete data so far on COVID-19 rebound, the second illness is typically mild, says the health advisory from the CDC. “There are no reports of severe disease,” even among those with compromised immune systems. And the public health agency said more treatment with Paxlovid or other antiviral therapies has not been needed in rebound cases.

According to CBS News, “Dr. Kevin O’Connor, Mr. Biden’s physician, said in a letter distributed by the White House that the president ‘continues to feel well as he starts his week.’ Mr. Biden’s positive COVID-19 antigen test, taken Monday morning, was ‘anticipated,'" as he had tested positive over the weekend.

Precautions, though, must be taken to avoid giving COVID-19 to others even in light-symptom rebound cases.

What is Paxlovid?

A Paxlovid prescription contains two types of oral antiviral pills: nirmatrelvir tablets and ritonavir tablets, a combination designed to reduce the risk of hospitalization and death for patients considered at risk of disease progression and severe illness. It’s available under emergency use authorization by the U.S. Food and Drug Administration for patients 12 and older, with a weight requirement of at least 88 pounds.

According to the CDC, Paxlovid is recommended for those who test positive, have mild to moderate illness, have a risk factor for serious illness from COVID-19 — including certain medical conditions, age or being immune-comprised — and don’t have impaired kidney or liver function. It has to be started within five days of symptom onset to be effective at reducing symptom severity.

In most cases, the health advisory said, the rebound illness gets better on its own within an average of three days without additional treatment, though patients are still required to isolate for the full five days. According to case reports, “COVID-19 rebound did not represent reinfection with SARS-CoV-2 or the development of resistance to Paxlovid; also, no other respiratory pathogens were identified among known cases,” the CDC said.

It’s not known how transmissible COVID-19 is during rebound. But experts believe COVID-19 is still contagious in those who are rebounding.

“People who experience rebound are at risk of transmitting to other people, even though they’re outside what people accept as the usual window for being able to transmit,” Dr. Michael Charness of the Veterans Administration Medical Center in Boston told CNN.

According to the article, “Charness and his colleagues recently collaborated with a team of researchers at Columbia University to look into cases of Covid-19 that return after Paxlovid treatment. He said they’ve found at least two instances in which people have transmitted to others when their infection recurs.”

Rebound cases, like initial cases, require isolating for at least five days. After that, a patient has to go 24 hours without fever or symptoms — without taking fever-reducing medication to suppress fever. And the patient should wear a mask for 10 days after the rebound symptoms started.

Although some people test positive longer than 10 days, after that long, they are “considerably less likely to shed infectious virus,” per the CDC.

Daniel Griffin, an infectious-disease expert, told The Atlantic’s Rachel Gutman-Wei that he thinks fewer than 10% of people who take Paxlovid rebound. And he doesn’t think those rebounds are related to the drug. “We’ve always seen this,” he said, noting that physicians treating patients with COVID-19 since 2020 have seen a pattern, especially among high-risk patients, that shows the illness getting worse for two weeks. “He suspects Paxlovid suppresses the first half of the illness; when that suppression stops, you get the ‘rebound,’” Gutman-Wei wrote.

Who Paxlovid helps

Paxlovid isn’t billed as a cure for COVID-19. Rather, it’s supposed to reduce symptoms so that people don’t end up in the hospital or dying from the illness, which has killed more than 1 million people in the United States, while more than 91 million cases have been confirmed, according to Our World in Data and The New York Times.

Researchers have tried to sort out who benefits the most from Paxlovid. For instance, Pfizer didn’t see a difference in terms of hospitalization between those who were unvaccinated and at low risk for serious illness based on factors like age and disease burden, compared to those who were high-risk on the criteria and vaccinated.

A study from Israel noted a 67% reduction in COVID-19 hospitalizations and an 81% reduction in COVID-19 death in patients 65 years old and older who were on the antiviral regimen. But it didn’t show a significant benefit in terms of avoiding COVID-19 hospitalizations in younger adults, where risks were already smaller.

A study from Hong Kong said Paxlovid was associated with fewer deaths, hospitalizations and in-hospital complications, compared to non-use of the prescription. And it noted some “protective effects” across vaccination status and age.