Closeup of man getting ready to take a pill with water

One in five people who take nirmatrelvir/ritonavir (Paxlovid) get COVID-19 again after the drug clears them of it, according to a new study.

For reference, people who didn’t take nirmatrelvir/ritonavir rebounded just 2% of the time, the authors noted. The news comes as the World Health Organization reclassified risk categories for COVID-19, a move that largely affects older adults otherwise thought to have a high risk for the condition.

Virologic rebound is the phenomenon of having a virus, receiving a negative test and then getting the virus again. Virologic rebound included people who tested negative after having the virus but then tested positive again as well as those who had two consecutive increases in viral loads following an initial reduction. 

Nirmatrelvir/ritonavir is an oral medication used to treat COVID-19. Previous research showed that 1% to 2% of people who took it had virologic rebound, but the new study indicates that getting COVID-19 again may be much more common than previously known.

Despite the findings, the team from Mass General Brigham said that the results don’t change the fact that the drug works to prevent hospitalizations and death. The study gives people who take the medicine valuable insights to understand how long they may be contagious, the authors said.

Their study was published Monday in Annals of Internal Medicine.

“We conducted this study to address lingering questions about Paxlovid and virologic rebound in COVID-19 treatment,” Mark Siedner, MD, an infectious disease clinician and one of the authors in the Division of Infectious Diseases at Massachusetts General Hospital, said in a statement

“We found that the virologic rebound phenomenon was much more common than expected — in over 20% of people taking Paxlovid — and that individuals shed live virus when experiencing a rebound, implying the potential for transmission after initially recovering from the virus.”

For the research, the team used data from the Post-vaccination Viral Characteristics Study, or POSITIVES. Data came from 142 people between March 2022 and May 2023. The researchers compared people who took nirmatrelvir/ritonavir with those who didn’t. They tracked the peoples’ symptoms and viral loads and conducted genome sequencing.

Of the participants, 20.8% who took nirmatrelvir/ritonavir had virologic rebound compared with 1.8% of those who didn’t take it.

People who had rebound had viral shedding — meaning they still were contagious — for an average of 14 days compared with five days in people who didn’t experience rebound. There wasn’t evidence of drug resistance among the people with prolonged shedding. 

In related news, the WHO announced updated COVID-19 treatment guidelines on Friday. The new guidance includes the addition of a moderate risk category and may include some people formerly thought to be at high risk. It includes older adults as well as those with chronic conditions, comorbidities and disabilities.