What Is Paxlovid Rebound? 9 Things to Know

[Originally published: Oct. 9, 2023. Updated: April 15, 2024]

Paxlovid is a pill that has proven to be effective at preventing severe disease from COVID-19. You start taking Paxlovid pills within the first five days of experiencing COVID symptoms (if you are 12 or older and at risk for serious disease), and it can protect you from getting so sick you need to be hospitalized.

One caveat is a reported “rebound” effect where, in the days after initial recovery from the disease, you either test positive again and/or experience a return of symptoms. This is sometimes called the “Paxlovid rebound.” Nobody knows for sure how common it is, and there is no strong evidence that Paxlovid causes it—a rebound has been reported by people who took the drug and those who didn’t. Because of this, the Centers for Disease Control and Prevention (CDC) calls the phenomenon “COVID-19 rebound” or, informally, "COVID rebound."

Scott Roberts, MD, a Yale Medicine infectious diseases specialist, is concerned less about the rebound than he is about how the phenomenon might affect people’s perception of Paxlovid, the first-line treatment for preventing severe illness from COVID-19.

“People may avoid Paxlovid out of a fear of COVID rebound,” Dr. Roberts says. “But for high-risk patients, the benefits of Paxlovid in preventing severe disease, hospitalization, and death far outweigh the downsides of a rebound, which is usually mild, and, in most instances, will do nothing more than prolong the isolation period.”

Studies have shown Paxlovid to reduce hospitalization and death by 86% in unvaccinated COVID patients (in initial trials by Pfizer, which developed the drug), and 80% effective in those who have been vaccinated. In November 2022, the CDC reported on a real-world study showing that adults who took Paxlovid within five days of a COVID diagnosis had a 51% lower hospitalization rate within 30 days compared to those who did not receive the drug.

What's more, Paxlovid should work against the Omicron subvariant JN.1, which is currently the dominant strain in the U.S. and has similarities to previous Omicron strains, adds Dr. Roberts. There is also evidence that it can decrease the risk of Long COVID.

Below, Dr. Roberts answers questions about COVID rebound.

COVID rebound is defined as a recurrence of COVID symptoms and/or receiving a positive COVID test after having the disease and then testing negative. It has been reported to occur between two and eight days after initial recovery, including in people who were “up to date” on their COVID vaccinations.

It’s characterized by a brief surge in symptoms that might last a few days. It’s different from Long COVID, which involves new, returning, or ongoing symptoms that can include a wide range of ongoing health problems and may last days, months, or even years.

The drug, available by prescription from health care providers and some pharmacists, is available to everyone ages 12 and older (weighing at least 88 pounds) who has mild-to-moderate disease and is at high risk for severe disease. It may help to talk to your doctor about the latter, which is a broad category covering diseases like diabetes, heart disease, and cancer; being age 50 or older; having obesity; or being a former or current smoker.

Paxlovid must be taken within five days of developing symptoms. You take three Paxlovid pills twice daily for five days for a full course (adding up to 30 pills). Paxlovid interacts with a long list of medications, including such common ones as cholesterol-lowering statins, so it’s important to talk to your doctor or pharmacist about other drugs you may be taking.

So far, researchers say there is no strong evidence of that.

The CDC notes in a health advisory that “a brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”

While it’s difficult to know how common COVID-19 rebound is, two studies of vaccinated people showed a rebound occurring in both patients who were given Paxlovid and those who got a placebo. Pfizer research showed a rebound in 2.3% of participants who took Paxlovid and 1.7% in the control group (where participants didn’t get the pill). In a different study, 14% of those who took Paxlovid experienced a rebound, and so did 9% of those who didn’t get Paxlovid.

“I believe 'Paxlovid rebound' is an outdated term that refers to the anecdotal experience of patients who report a rebound after Paxlovid treatment,” Dr. Roberts says.

Scientists are still studying the phenomenon. In the meantime, researchers are focusing on the effects of longer treatment durations, longer isolation periods, and other ways of managing the problem, Dr. Roberts adds.

“Most rebounds are mild—in fact, much milder than the initial peak COVID symptoms,” Dr. Roberts says. The symptoms are usually similar, but milder, to those the person had when they had COVID. The CDC has reported no increased occurrence of hospitalization or death in people with COVID rebound.

“If someone has recovered from COVID and does not have rebound symptoms, I would not recommend routine antigen testing,” Dr. Roberts says.

People who have been diagnosed with COVID should follow CDC guidance, which includes staying home and away from others until, for 24 hours, they are both fever-free (without medication) and their symptoms are getting better. “If symptoms get worse after the initial improvement, then it may be worth repeating a rapid test to see if it is positive and consistent with a rebound case,” he says.

People experiencing COVID rebound after treatment can be contagious. Experts warn that people who have COVID rebound without symptoms may also be contagious and not realize it.

No, a rebound does not mean Paxlovid didn’t work, Dr. Roberts says, explaining that the major goal of Paxlovid is to decrease the risk of severe disease in high-risk individuals. “If that comes at the cost of a potential COVID-19 rebound, which is usually mild, I would accept that trade-off to avoid hospitalization or worse,” he says.

You can’t predict or prevent COVID rebound. If you have recovered from COVID but have tested positive or are experiencing symptoms again, you should restart isolating and masking, following CDC recommendations. “There is no evidence that additional treatment is needed or will help cases of COVID rebound, so treatment is not recommended in a rebound case,” Dr. Roberts says.

Pfizer recommends anyone who experiences COVID rebound report it on its portal for adverse events associated with Paxlovid.