Covid-19 rebound may be more common in people taking Paxlovid, early study finds


Rebound cases of Covid-19 after treatment with the antiviral drug Paxlovid – where infections come back after people have completed their five-day course – appear to be at least twice as common as doctors previously knew, according to a new study. Covid-19 rebound also appears to be more common in people taking Paxlovid than in those not taking the antiviral, although it can happen in either case.

Over the past few months, rebounding cases of Covid-19 have been in the headlines. President Joe Biden, first lady Jill Biden, as well as Dr. Anthony Fauci, who advises the president on pandemic strategy and Dr. Rochelle Walensky, director of the US Centers for Disease Control and Prevention, have all revealed that their Covid-19 infections returned after they finished taking Paxlovid.

“Worst. Continued. Ever,” comedian Stephen Colbert joked on Twitter after his May bounce case.

These high-profile cases have led to speculation on social media that rebounding may not be as rare as some studies have concluded. So far, studies have suggested that around 5% of people who take Paxlovid will experience a rebound.

In June, Pfizer, the company that makes Paxlovid, published an analysis of data from clinical trials of the drug showing that Covid-19 infections returned both in the group that received placebo pills and in those who took Paxlovid, somewhere between 2% and 7% of the time. This study found that rebounding occurred about twice as often in people taking Paxlovid as in those taking the placebo.

Another study in June, conducted by researchers at the Mayo Clinic, reported that only four out of 483 patients – less than 1% – who took Paxlovid experienced a return of their Covid-19 symptoms after treatment.

Most rebound studies have had one significant weakness, however: They have looked at patient records, looking back in time, to count cases that recur.

This approach probably underestimates the true number of people who experience this phenomenon because there are missing people who rebound at home and have no symptoms with their rebound – they are positive again in a rapid test – or have symptoms so mild that they don’t. I don’t feel the need to go back to see a doctor.

The new study, led by researchers from the Scripps Research Translational Institute and telehealth company eMed, has a significant advantage in this regard. It is one of the first to track Covid-19 patients over time to measure returning cases.

The study included 170 patients who came to eMed for testing and who were deemed by their doctors to be eligible to take Paxlovid because they were at high risk of developing severe symptoms of Covid-19.

They were invited to join the study only after they had decided whether they wanted to take Paxlovid, the study’s lead author, Dr. Jay Pandit, director of digital medicine at Scripps, said in an interview with CNN.

“We didn’t want to bias or influence their decision to take Paxlovid or not,” Pandit said.

The study also has important limitations that make its conclusions imprecise. It’s just getting started, so these early results come from a relatively small group of early enrolled patients – 127 who took the drug Paxlovid and 43 people who were eligible to take it but declined. These 43 people served as the comparison group.

The study does not have enough statistical power to say whether the observed differences between the two groups were due to chance or to the treatment. The researchers say they eventually hope to recruit a total of 800 people, a study size that should yield clearer answers.

After people agreed to take part in the study, they received a kit containing 12 rapid home tests. They were advised to test every other day. They were also asked to answer questions about their symptoms.

Of the 127 who took Paxlovid, about 14% saw their viral load rise after treatment. This group tested positive for Covid-19, tested negative after completing their 5-day course of Paxlovid, and then tested positive again a few days later. Around 19% saw their symptoms return after completing their Paxlovid treatment although they may not have tested positive again.

Some of the people in the comparison group also experienced rebound – although this seemed to be less common for these patients compared to the group that took Paxlovid. About 9% of the 43 people in this group tested positive again after initially clearing the infection and about 7% of them reported that their symptoms had returned.

So far, Pandit said, the study shows two main things: as many have suspected, Covid-19 rebound appears to be more common than previous research suggested; rebound may also occur whether or not you take Paxlovid.

“The incidence rates [reported by previous studies] have had huge varying numbers, and most of them tend to be single digits,” Pandit said. “The message really is that we are seeing a higher number of incidents,” he said.

The study was published as a preprint, ahead of peer review.

Researchers who weren’t involved in the study agreed it was on the right track and said the numbers it collects will firm up over time. This should also help answer the question of whether rebounding is really more common after taking Paxlovid.

“There is an indication that symptom rebound is more common in Paxlovid-treated participants than in untreated controls, but larger numbers are needed to draw reliable conclusions,” said Dr. Michael Charness, Chief of Staff of the VA Boston Healthcare System. Charness has documented instances of Paxlovid rebounding, including his own.

Pandit says they will continue to follow study participants and plan additional rounds of testing to try to answer other lingering questions such as “why is the rebound happening in the first place?” And is it possible to avoid rebound by adjusting the dosage or duration of treatment? Does the rebound have anything to do with the long Covid? ”

Currently, there is no consensus on what should be done in the event of a rebound.

At least one study has documented a case of a person with rebound Covid-19 who took Paxlovid and transmitted the infection to an infant.

Typically, rebound cases are mild and resolve within a few days. Fear of a rebound shouldn’t stop anyone from taking the drug in the first place, Pandit says.

“There is a lot of under-prescription of Paxlovid. We know it reduces hospitalization rates, reduces symptom progression, we know that, and we don’t want to fuel the fire of underprescribing,” Pandit says.

In clinical trials, Paxlovid was nearly 90% effective in preventing hospitalizations and deaths in high-risk patients. As the virus evolves to beat other types of treatments, Paxlovid has continued to work.

Similarly, says Pandit, uncertainty about rebound almost certainly makes people hesitant to use the drug. Studying rebound, he says, should shed important light on the problem and help equip people with knowledge.

“We need to understand that one of the causes of underprescribing is this misunderstanding of what the incidence rates really are,” he said. “It’s something we need to look at, so we can counter it.”


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