No ‘COVID rebound’: Few patients taking Paxlovid experience relapse, study says

ROCHESTER, Minn. — The fears of a “COVID-19 rebound” among patients taking Paxlovid appear to be exaggerated, a new study reveals. Researchers at the Mayo Clinic found that less than one percent of patients taking the coronavirus treatment saw their symptoms return days or weeks later.

Specifically, just four high-risk COVID patients out of 483 taking the five-day oral regimen of nirmatrelvir and ritonavir — which together form the drug Paxlovid — experienced COVID-19 “rebound symptoms” between six and 19 days after their treatment. Moreover, all of these individuals had serious pre-existing health issues that put them at higher risk for severe COVID complications.

What is a COVID-19 rebound?

Doctors say this phenomenon occurs when a COVID patient recovers and tests negative for the virus, only to retest positive or develop COVID-like symptoms days or weeks later.

Recent reports have linked Paxlovid to a higher chance of experiencing this rebound. The CDC even sent out an advisory in May 2022, warning that patients taking Paxlovid could see their symptoms return. Those fears appear to have been premature, according to the new study.

Out of the 483 patients, all of them benefited from the five-day treatment. Each person recovered, including the four experiencing rebound symptoms. Moreover, the team reports these rebound symptoms were generally mild.

“We found that rebound phenomenon was uncommon in this group of patients,” says senior author Aditya Shah, M.B.B.S., a Mayo Clinic infectious diseases physician and researcher, in a media release. “The four individuals who experienced rebound (symptoms) represent only 0.8% of the group, and all of them recovered quickly without additional COVID-directed therapy.”

Researchers add that most of the patients in their study were vaccinated and many already received boosters. The average age of the group was 63. Although each person fell into the high-risk category for COVID infection, none qualified as immunocompromised.

Who experienced a COVID rebound?

A closer look at the four individuals who did have a COVID-19 rebound found all of them had pre-existing conditions which generally put someone at a higher risk of a severe case of the virus.

  • A 75-year-old man with coronary artery disease experienced increased coughing and muscle aches 19 days after taking Paxlovid.
  • A 40-year-old woman with obesity, hypertension, and kidney disease developed fatigue and a sore throat 6 days after treatment.
  • A 69-year-old man with hypertension and obesity developed nasal discharge and coughing 10 days after treatment.
  • A 70-year-old man with prostate cancer, obesity, hypertension, and high cholesterol experienced severe sinus congestion 10 days after treatment.

So, why did these patients have a rebound? Researchers say one explanation is that the SARS-CoV-2 virus replicated and triggered a second immune response — resulting in mild symptoms. The team also notes that even though each of these four people received the COVID-19 vaccine, they all had comorbidities which can complicate their recovery from COVID.

The findings appear in the journal Clinical Infectious Diseases.

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About the Author

Chris Melore

Chris Melore has been a writer, researcher, editor, and producer in the New York-area since 2006. He won a local Emmy award for his work in sports television in 2011.

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