Paxlovid Rebound: CDC Warns of COVID-19 Symptom Recurrence

Fact checked on June 1, 2022 by Vivianna Shields, a journalist and fact-checker with experience in health and wellness publishing.

Some patients who have taken Pfizer's Paxlovid medication—an antiviral drug used to prevent severe illness from COVID-19—have experienced a recurrence in their symptoms in the days after completing the treatment.

In a Health Advisory issued by the Centers for Disease Control and Prevention (CDC) on May 24, officials warned health care providers, public health departments, and patients on the potential for a "COVID-19 rebound," sometimes known as "Paxlovid rebound"—but maintains that the treatment is still essential for many with the virus.

"Paxlovid continues to be recommended for early-stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease," the statement said, adding that people who experience a COVID-19 rebound after Paxlovid treatment "have had mild illness" and there are no reports of severe disease.

Here's what to know about COVID-19 recurrence following Paxlovid treatment.

COVID-19 Rebound, Explained

Paxlovid is an antiviral medication used to treat COVID-19 in people with mild to moderate illness, and who are at risk for severe disease. The medication—which actually consists of three separate pills, all taken at the same time—is meant to be taken twice a day for five days.

According to the CDC, a COVID-19 rebound is a recurrence of COVID-19 symptoms or a new positive viral test (after previously testing negative), within two to eight days after recovery and stopping Paxlovid. This can happen regardless of vaccination status.

"Typically, what people are reporting is that the relapse in symptoms are similar or maybe slightly better than what the original symptoms were that individuals had, but it is a recurrence," infectious disease specialist Prasanna Jagannathan, MD, assistant professor of medicine and of microbiology and immunology at Stanford University, told Health. "Folks feel better and then they feel worse again."

It's unknown exactly how many people experience a COVID-19 recurrence after Paxlovid. In clinical trials, about 1%–2% of patients experienced a COVID-19 rebound case—but anecdotal evidence and new preliminary studies suggest the phenomenon could be happening to a larger population.

Symptoms of COVID-19 Rebound

If COVID-19 symptoms recur following Paxlovid treatment, they're typically mild and resolve in about three days, the CDC said.

In a recent preprint case report, researchers described the COVID-19 relapse symptoms of eight non-immunocompromised people ages 31–71. The relapse of COVID-19 symptoms—which usually occurred on days nine through 12 of their illness—were described as cold symptoms (runny nose, sore throat), as well as fatigue and headache.

In six of the eight people, relapse symptoms were milder than initial COVID-19 symptoms—which, according to experts, is typical of COVID-19 rebound cases.

"In my experience in the ER, these brief returns of symptoms tend to be milder symptoms such as a runny nose, headache, sore throat, or changes in stools," Arjun Venkatesh, MD, associate professor of emergency medicine and chief of administration in emergency medicine at Yale Medicine, told Health.

There have also been no reports of severe disease due to COVID-19 relapse, the CDC said.

Why Do COVID-19 Rebounds Happen?

The CDC confirmed that COVID-19 rebounds were not due to reinfection by the SARS-CoV-2 virus or resistance to Paxlovid—but experts still aren't entirely what's behind relapses after stopping medication.

According to Dr. Jagannathan, one possible explanation is that low levels of the virus may persist in the body, and are able to multiply again once an individual stops treatment. "That is the most likely answer, but we still don't know," said Dr. Jagannathan.

In the CDC's statement, the agency also said that "a brief return of COVID-19 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.

Researchers are also looking into any factors that may predispose individuals to COVID-19 rebounds, but there's no clear trend there, either. "At this point, it appears to be pretty random," said Dr. Jagannathan, noting that this phenomenon has been observed in both young and old patients, and immunocompetent and immunocompromised people.

What to Do During a COVID-19 Rebound

According to the CDC, there is no evidence that suggests any additional treatment is needed for a COVID-19 recurrence, since the symptoms seem to be short-lasting and self-limiting.

"Based on the data, a single course is enough to get the desired effect—namely reducing your chance of severe COVID-19 that causes hospitalization or death," said Dr. Venkatesh. Though some researchers are looking into potentially extending Paxlovid courses, the CDC maintains that there's no data currently that suggests this may be helpful.

But people who experience COVID-19 rebounds should still re-start their isolation period once their symptoms recur or they receive another positive test, according to the CDC. The guidance is based on another preliminary case report, which found that one symptomatic and one pre-symptomatic patient with relapsing COVID-19 transmitted the virus to family members.

"The presence of high viral load and the occurrence of two transmission events suggest that the patients with relapse should isolate until antigen testing is negative," study authors wrote.

Relapsing COVID-19 patients can end their second isolation period after five days if their symptoms are improving and they haven't had a fever in 24 hours—but they should still continue to wear a mask around others for five additional days, to complete the CDC-recommended 10 days of isolation and masking.

Both health care providers and patients are encouraged to report any possible COVID-19 rebound cases following Paxlovid treatment to Pfizer using the Pfizer Safety Reporting online tool.

Despite the possibility of recurrence following Paxlovid treatment, health care providers maintain that the drug is essential in treating people who are at high risk of severe disease from COVID-19, and should continue to be prescribed and used. "If you are someone who meets the criteria to receive Paxlovid as stipulated in the EUA," said Dr. Jagannathan, "I would strongly recommend that person taking it because of the clear benefits in preventing disease and hospitalization."

The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDC, WHO, and their local public health department as resources.