What should people know about Paxlovid rebound? Our medical analyst explains

By Katia Hetter, CNN

After being diagnosed with Covid-19 last month, President Joe Biden recently tested negative for the coronavirus, only to test positive again a few days later. Biden had taken the antiviral medication Paxlovid, which has been associated with some patients testing positive again for the virus after completing treatment.

This phenomenon is known as Paxlovid rebound. What is it exactly, and why does it happen? How common is it, and does the possibility of a recurrence of symptoms mean that people shouldn’t take it? Who should and shouldn’t take the drug? And what should you do if you do have a recurrence?

To guide us through all these issues, I spoke with CNN Medical Analyst Dr. Leana Wen, an emergency physician and professor of health policy and management at the George Washington University Milken Institute School of Public Health. She is also author of “Lifelines: A Doctor’s Journey in the Fight for Public Health.”

CNN: What is Paxlovid rebound, and why does it happen?

Dr. Leana Wen: The phenomenon known as Paxlovid rebound is what happens when someone with Covid-19 takes the antiviral pill Paxlovid and begins to recover — their symptoms improve, and they start testing negative. Then, usually within two weeks of their initial diagnosis, they have a recurrence in their symptoms, and they test positive for the coronavirus again. In President Joe Biden’s case, he was being tested regularly, so even though his symptoms didn’t recur, his positive test was picked up right away.

It’s not known exactly why this is occurring. A small study out of the University of California, San Diego found that this isn’t due to Paxlovid being rendered ineffective against variants. The very small window of time when it happens also suggests this is not due to reinfection. Rather, a lot of scientists, including me, think that this is most likely due to Paxlovid working as it should but not for long enough.

Paxlovid works to stop viral replication. It is currently given for five days. Perhaps it works for the five-day period, but some people still have virus in their body after five days. When Paxlovid is stopped, the virus starts replicating again.

It’s possible that Paxlovid may need to be given for a longer period of time — maybe seven or 10 days instead of five days. Those studies are ongoing.

CNN: It seems like a lot of people have Paxlovid rebound, including President Biden and Dr. Anthony Fauci. How common is it?

Wen: Anecdotally, we may know a lot of people who’ve had it, but studies show that it’s pretty uncommon.

The initial studies found that rebound occurred in about 2% of cases. By the way, those who did not take Paxlovid also had a chance of recurrence. In that study, the placebo group had a recurrence of symptoms in 1.5% of cases.

Those studies were done during a time when the Delta variant was the dominant variant. The rates of rebound may be higher during Omicron. A large study of over 13,000 patients done by researchers from the National Institutes of Health found a rebound rate of about 6%. Note that this study is online but not yet peer-reviewed.

Of course, the actual rate may be higher, because people are not routinely being tested after they take Paxlovid. Some cases may be missed as a result. However, it still seems that Paxlovid rebound is occurring in a minority, not majority, of cases.

CNN: Does the possibility of a recurrence of symptoms mean that people shouldn’t take it?

Wen: No. I think people should consider the possibility of Paxlovid rebound like a known side effect of the medication. It’s certainly not preferred to have this, given the inconvenience of having repeat symptoms and having to isolate again. However, the possibility of this side effect is not a reason to avoid a medication that is highly effective at reducing severe illness.

This comes down to why Paxlovid is given in the first place. It is an oral medication, prescribed so that people can take it at home, that can reduce the likelihood of being hospitalized or dying by nearly 90%. Neither Fauci nor Biden got severely ill. That’s the success story here — and the reason why people eligible for Paxlovid should still take it despite the possibility of rebound.

CNN: Who is eligible for Paxlovid? Are there people who shouldn’t take it?

Wen: The people eligible for Paxlovid are individuals who are vulnerable to severe outcomes if they were to contract Covid-19. The US Centers for Disease Control and Prevention has a list of these conditions. They include older age and chronic underlying medical problems such as heart disease, lung disease, diabetes and obesity. People who remain unvaccinated are at higher risk for severe Covid-19, too.

There are certain medical conditions people may have that either exclude them from taking Paxlovid, or they have to take a different dose. Some medications also interfere with Paxlovid and may need to be stopped for a short time. That’s why it’s critical to check with your physician. I encourage you to check with your health care provider, even if you haven’t contracted Covid-19, to know whether you are eligible for Paxlovid.

As far as people who shouldn’t take it, Paxlovid is intended for individuals at high risk for severe disease. If you are under 50, up to date with vaccines and generally healthy, you should not take it. Every medication is about weighing risks and benefits. If you are unlikely to benefit, the risks will outweigh the benefits.

CNN: What should you do if you do have a recurrence — do you take Paxlovid again, and do you need to isolate?

Wen: Paxlovid rebound is very unlikely to progress to severe illness, as a recent CDC report found. It is not currently recommended to take Paxlovid for rebound cases, though this is a recommendation that could change as more studies are under way. (Fauci’s doctors prescribed another course of Paxlovid.)

The CDC does say that individuals with rebound infections should isolate for another five days. That’s because an individual who is testing positive again by rapid home antigen test is shedding virus and could still be contagious to others.

Using caution is the right approach, but I want to emphasize again that the possibility of rebound should not dissuade people from taking a treatment that is doing what it should, which is to keep people out of the hospital and preventing them from getting severely ill.

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