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Some people are experiencing 'Paxlovid rebound' after taking the COVID antiviral pill. Here's what you should know.

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Paxlovid pill box with three pills printed with PFE and R9 on it.

Paxlovid is Pfizer’s antiviral drug to treat COVID-19. (Reuters/Wolfgang Rattay/Illustration)

Yahoo News explains.  See the latest.

When the antiviral drug Paxlovid was approved in 2021 to treat COVID-19, doctors began to notice a disconcerting trend among some of the patients taking the drug: a rebound case of the virus. After treatment, some people would recover and test negative for the virus, only to test positive or symptoms would return a few days later. The “Paxlovid recovery,” as it is known, received a lot of media attention when President Biden, First Lady Jill Biden, and Drs. Anthony Fauci and Rochelle Walensky, director of the Centers for Disease Control and Prevention, experienced this last year after taking the drug.

Scientists aren’t sure why this rebound effect occurs when taking Paxlovid, but here are some things we do know.

What is Paxlovid? How it works?

Paxlovid is an oral antiviral pill that can be prescribed for people who contract COVID-19 and are at risk of developing serious illness. These may be unvaccinated individuals, the elderly, or people with other medical conditions such as cancer or diabetes. The drug, developed by Pfizer, could protect these high-risk patients from needing hospitalization. Those who are vaccinated but are at risk of serious outcomes from COVID-19 may also benefit from taking Paxlovid.

US regulators granted emergency use authorization to Paxlovid in December 2021. Today, the drug is only available with a prescription, from a doctor or pharmacist. Anyone age 12 and older who weighs at least 88 pounds and who is at high risk of serious illness is eligible for the drug. Patients with severe kidney disease – or who are on dialysis – or people with severe liver disease, however, should not take Paxlovid. The drug can also interact with other medications, such as those that treat high cholesterol, high blood pressure, and migraines, so patients taking these medications should avoid taking Paxlovid.

Like many antivirals, Paxlovid works best when taken early in the illness. The CDC recommends that treatment begin within the first five days of symptoms. After a person receives the medication, they take three Paxlovid pills twice a day for five days for a full course that totals 30 pills.

Antiviral therapy consists of a combination of two oral antiviral drugs – nirmatrelvir and ritonavir – that work together to stop the viral replication process. By reducing a person’s viral load, the drug lessens the severity of their symptoms.

In clinical trials, conducted when the Delta variant was predominant, Paxlovid reduced the risk of hospitalization or death by 89% in high-risk people. Since its approval, many clinical studies conducted around the world have also confirmed the drug’s high level of protection against hospitalization and death.

With Omicron being a highly evasive variant of the immune system that has rendered many antibody treatments ineffective, vaccine experts feared that Paxlovid would also lose its effectiveness. Fortunately, that doesn’t seem to be the case. According to recent research, the drug continues to offer significant protection against hospitalization and death and may also offer substantial benefit even for vaccinated patients diagnosed with COVID-19.

Other studies, however, have found no evidence that Paxlovid benefits people younger than 65.

“I don’t think we need to push Paxlovid on every 20-year-old who gets COVID or 35-year-olds who are healthy,” Dr. Bruce Farber, chief of public health and epidemiology at Northwell Health, the largest health care system in New York state, told Yahoo News. “But in those at high risk, elderly, unvaccinated, with comorbidities, immunosuppressed, [for] those people [it] can make a significant difference,” he added.

In addition to preventing high-risk patients from getting very sick, Paxlovid may reduce the risk of prolonged COVID symptoms, found a November study conducted by the Department of Veterans Affairs.

What is Paxlovid rebound?

The CDC defines Paxlovid rebound as when, after completing the full five-day course of treatment, a person experiences a resurgence of symptoms or tests positive after having tested negative for COVID-19. According to the CDC, this rebound effect tends to occur between two and eight days after initial recovery. But experiencing a recovery, the agency said, does not mean a person was resistant to Paxlovid, nor does it mean they were reinfected with the virus. Additionally, the CDC said that cases of Paxlovid rebound are generally mild, resolve within a few days, and there is no evidence that additional treatments are needed for these patients.

Despite Paxlovid’s effectiveness even in the context of Omicron, the drug is being underutilized in the United States and other parts of the world. According to a report by London-based health analytics firm Airfinity, US doctors prescribed the drug in only about 13% of new COVID-19 cases, Nature recently reported. Experts have said that concern over Paxlovid’s possible rebound is one of the reasons this could be happening.

Farber also said that another reason Paxlovid is being underutilized has to do with the virus itself.

“This virus is much less virulent, although it is more contagious,” he said, adding that the need for Paxlovid “has become less.”

Scientists are still studying why this rebound effect occurs when taking Paxlovid, as well as who is most likely to experience it. However, recent research has found that rebound can also happen to people who develop COVID-19 and do not take Paxlovid. Studies are underway to understand why this happens, Farber said.

“More recent data suggest that rebound also occurs in people recovering from COVID who did not receive Paxlovid, and it likely occurs at similar rates regardless of whether you take Paxlovid or not,” Farber said, adding that cases of rebound after taking Paxlovid medicine were initially thought to occur in about 5% of cases, but this research has shown that it can happen more often than initially thought. “More recent papers say it could be as common as 10 or 15% of cases,” he said.

What to do if you experience Paxlovid rebound

If someone’s symptoms return or test positive after treatment with Paxlovid, the CDC advises following their isolation guidance and re-quarantining for five days. Isolation may end after this period if the person has been fever-free for 24 hours without the use of fever-reducing medication. The agency also recommends wearing a mask for 10 days after the onset of rebound symptoms.

The CDC encourages physicians and patients to report cases of Paxlovid rebound to the Pfizer portal for drug-associated adverse events.

Finally, Farber said that Paxlovid’s rebound is still quite uncommon and that it shouldn’t deter people and their doctors from using the life-saving drug when needed.

“In theory, this could prolong the isolation. But I think [people] must realize that this can occur even without Paxlovid. So it really becomes an important badge whether they understand it or not,” he said.