As Covid cases crept up over the summer and new variants have emerged, the basics of preventing and managing the virus have come back into focus — including a critical tool for warding off severe disease and death: the antiviral treatment Paxlovid.
The therapy, which consists of two medications, is intended for people who are at high risk for developing severe disease. According to the Centers for Disease Control and Prevention, this is a fairly broad category, including people with mood disorders like depression, current and former smokers and those with obesity.
Experts stress that Paxlovid is an effective, lifesaving treatment that helps to keep people out of the hospital. It may even lower the risk of developing long Covid. But the medication has gotten a bad reputation from high-profile instances of “Paxlovid rebound,” or testing positive days after recovering from the virus, said Dr. Peter Chin-Hong, an infectious disease specialist at the University of California, San Francisco.
While Paxlovid rebound is well documented, it’s also possible to experience a resurgence of symptoms even if you don’t take the drug. A representative from Pfizer wrote in an email that rebound is “uncommon and not uniquely associated with any specific treatment.”
Rebound is a tricky concept to pin down, partly because you can define it in two ways: by looking at whether someone tests positive again a few days after testing negative, or by looking at whether symptoms have returned after someone has seemingly recovered. It’s also hard to differentiate between rebound symptoms and those that simply linger — or those of long Covid.
“It’s a muddle,” said Jay Pandit, the director of digital medicine at the Scripps Research Translational Institute.
As a result, it’s hard to quantify how often rebound occurs. In a clinical trial, Pfizer researchers estimated that 2.3 percent of people who took Paxlovid and 1.7 percent of the control group experienced a rebound, but outside research has shown that the rate may be as high as around 14 percent for those who took the drug, and around 9 percent for those who did not.
It’s hard to get real-world data because many people who have a rebound are unlikely to tell their doctors, said E. John Wherry, director of the Institute for Immunology and Immune Health at the University of Pennsylvania Perelman School of Medicine.
“The numbers are definitely higher than what have been reported,” said Dr. Michael Mina, a former Harvard epidemiologist who is now the chief science officer for eMed, a telehealth company, and who has studied rebound.
Why does Covid rebound happen?
The theory behind Paxlovid rebound is that the treatment is so effective at suppressing the virus that the immune system does not ramp up its cellular and antibody defenses the way it typically would. It’s like allowing the medication to take the steering wheel from your immune system.
“Your immune system was going to take a back seat for a little bit, and then you’re asking it to kick in after five days of treatment,” Dr. Mina said. After you complete the treatment, the virus can replicate in your nose again, sometimes with a vengeance.
But it’s not totally clear why symptoms can also reappear after a negative test even without taking Paxlovid, Dr. Mina said. The immune system has two jobs: to quash the virus and repair the body. It’s possible that the immune system goes into its restorative mode too early in some people, he said, giving the virus a chance to replicate before it’s fully destroyed.
Beyond that, though, it’s not yet understood why some people might be more likely than others to get rebound, Dr. Chin-Hong said.
I’m positive (again.) What do I do now?
Rebound typically occurs within a week of recovering from the virus, Dr. Pandit said. It’s possible, although rare, to experience rebound without developing symptoms, he added.
It’s not clear just how contagious people are when they rebound. But if you test positive again on a rapid test, assume that you’re contagious, Dr. Mina said, and take the necessary precautions: Isolate from other people as much as possible, and wear a high-quality mask if you go out in public or are around household members. The C.D.C. estimates that rebound lasts, on average, three days, but this can vary — in some people, it lasts two days, and in others, it can stretch on for 10.
Rebound cases tend to be milder than the original course of infection, and people typically do not take another course of Paxlovid if they experience a rebound. But it’s important to monitor your symptoms, Dr. Pandit said, and to reach out to a doctor if they become severe.