Covid-19 rebound affects one in five people after taking Paxlovid

Paxlovid, which is made up of the drugs nirmatrelvir and ritonavir, can stop the SARS-CoV-2 coronavirus from spreading in the body

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Just over one in five people who take the covid-19 drug Paxlovid may be contagious after coming off the treatment, but doctors say this isn’t a reason to stop prescribing it.

In a recent study, people who took Paxlovid, which is made up of the medicines nirmatrelvir and ritonavir, were just over 10 times more likely to experience “covid-19 rebound” – when the virus increases in the body after an initial decrease – compared with those who didn’t take it, suggesting that the former group may still be contagious post-treatment.

Paxlovid can reduce covid-19-related hospitalisations and deaths by stopping the SARS-CoV-2 coronavirus from growing in the body. Although often effective, many people have reported covid-19 rebound after coming off the drug.

“We knew it was an actual public health issue; what we didn’t really know was how common it was,” says Mark Siedner at Massachusetts General Hospital.

To learn more, Siedner and his colleagues tracked the symptoms and viral loads – the amount of the virus in swabs – of 127 people with mild to moderate covid-19. Of these, 72 took a five-day regimen of Paxlovid.

Over the study, which lasted nearly a year, the researchers found that 20.8 per cent of those who took Paxlovid went on to have covid-19 rebound, compared with 1.8 per cent who didn’t have any treatment or a placebo. The team defined this rebound as a drop in viral load followed by two consecutive increases within a 20-day period.

Covid-19 rebound wasn’t associated with developing more severe symptoms. The researchers didn’t measure whether the participants infected others during their rebound, but wrote in their paper that having relatively mild symptoms or none at all means people could be contagious without realising it.

The findings shouldn’t stop doctors from prescribing Paxlovid, but its potential risks and benefits should be considered for each individual, says Siedner. Exactly why this rebound can occur with Paxlovid is unknown, but it might be because some people need more than five days of treatment, the standard dosing regimen, he says.

The latest research comes after certain studies, some of which were carried out by Pfizer, Paxlovid’s manufacturer, suggest that rebound isn’t specific to this treatment. The differences in results between trials appear to be due to varying sampling times, says Siedner.

In the latest study, people were tested three times a week and their viral samples were assessed for the pathogen’s ability to replicate. In some of the previous research, testing occurred on only three days and didn’t include this assessment, says Siedner.

“We are continuing to monitor the data, but believe viral rebound is relatively uncommon and not uniquely associated with any specific treatment,” says a Pfizer spokesperson. “We remain very confident in Paxlovid’s clinical effectiveness at preventing severe outcomes from covid-19 in patients at increased risk.”

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