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Paxlovid rebound: What you need to know about COVID return

Some HIV-positive coronavirus patients who have finished treatment with the COVID drug Paxlovid are relapsing, and experts are urging people to be cautious if they develop COVID-like symptoms again.

It’s not clear how often “post-Paxlovid rebound” occurs, but Dr. Robert Wachter, chairman of the Department of Medicine at UC San Francisco, said he knows of at least one person who finished Paxlovid treatment and then he became infected again, spreading the virus to other members of his family.

“It can happen,” Wachter tweeted. “If you develop recurrent symptoms and have a rapid test [positiva], it is infectious. Please act accordingly.”

Los Angeles County Public Health Director Barbara Ferrer said relapses of COVID-19 after Paxlovid are “real.”

“They have occurred in significant enough numbers that they have been noticed by a lot of people in a lot of different places,” he said.

The Food and Drug Administration (FDA) has authorized the use of Merck’s molnupiravir pill for the treatment of COVID-19. The molnupiravir pill is licensed for use in adults 18 years of age and older who have tested positive for COVID-19 and are at high risk of being hospitalized or dying.

In a statement on its website, the US Food and Drug Administration said it is aware of reports of COVID-19 symptoms returning after completion of Paxlovid treatment. “In some of these cases, patients tested negative on a direct viral test for SARS-CoV-2 and then tested positive again,” the FDA said.

The agency said that in the Paxlovid clinical trial, there have been some patients — about 1% to 2% — who tested negative and then tested positive. The finding occurred not only in people who took Paxlovid, but also in those who took the placebo.

“However, judging by all the anecdotes, rebound seems more common than you think; we are waiting for good data,” Wachter tweeted.

Wachter suggested that a person who has completed Paxlovid treatment and then tests positive should be considered infectious.

Those who want to be especially careful about the risk of infecting others may consider wearing a mask in all indoor settings, even around family members from the same household, for a few more days or maybe a week once Paxlovid treatment is complete, Wachter said.

Even a negative rapid test after completing five days of Paxlovid treatment can provide false assurance that a person is not contagious. A negative rapid test result suggests that a person is probably not infectious, but there is still a small chance — perhaps 1% — that a person in this situation could test negative and still be contagious, Wachter wrote.

“Wearing masks for a few more days seems reasonable if you’re careful,” he said.

The rebound of COVID-19 after Paxlovid still appears to be unusual, Wachter said, and not harmful to the recovering patient. Wachter said the rebound news shouldn’t discourage people from taking Paxlovid, given its high rate of efficacy against severe illness and death.

Data has shown that Paxlovid, made by Pfizer, reduces the risk of hospitalization or death from COVID-19 by 89% among highest-risk adults.

Furthermore, it is plausible, but not proven, that “rapidly reducing viral load (which Paxlovid does) could decrease the risk of long-lasting COVID and make people less infectious,” Wachter wrote.

The FDA agreed that reports of the rebound of COVID-19 after Paxlovid do not change scientists’ general opinion that the drug is highly effective.

“Most importantly, there has been no increase in hospitalizations or deaths or the development of drug resistance,” the FDA said. “These reports therefore do not change the conclusions of the Paxlovid clinical trial, which demonstrated a marked reduction in hospitalization and death.”

The FDA noted that patients should wear a mask and stay home and isolate if they have any symptoms of COVID-19, regardless of whether they have been given an antiviral drug such as Paxlovid.

A report by scientists at the University of California, San Diego published online Wednesday looked at the history of a traveler who returned to the US after a trip to South Africa and had recurrent COVID-19 after completing a course of Paxlovid. The scientists said the most likely possibility for the recurring symptoms was “insufficient exposure to the drug.”

Among those who watched the rebound was Dr. Paul Sax, an infectious disease expert at Harvard Medical School, who recounted in a recent blog post how a COVID-19 patient recovered quickly after taking Paxlovid, but a week later he called him saying he had relapsed. Although the symptoms were not as severe as her initial illness, rapid test results showed that she was “clearly positive again.”

“His biggest concern was getting back out into the world without infecting anyone. She really wasn’t that sick; she just wanted advice on when she could go back to work and start socializing again,” Sax wrote. “‘Avoid close contact with other people until you are tested,’ I told him.”

The patient made a full recovery, and started testing negative a few days later, Sax wrote.

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