One of the most effective medicines against severe covid-19 may not eradicate the virus in everyone. Several countries – including the US, UK, Canada, Israel and France – may prescribe a five-day course of the Pfizer drug Paxlovid, which can be taken at home, to people who are particularly vulnerable to covid-19’s complications.
In the trial that led to its approval, Paxlovid cut the risk of a covid-19-related hospitalisation or death by 88 per cent. But emerging reports now suggest that a small number of people experience a resurgence of symptoms after finishing the five-day course.
Paxlovid consists of a drug called nirmatrelvir, which stops the SARS-CoV-2 virus replicating, and a drug called ritonavir, which slows the breakdown of nirmatrelvir in the liver. In the UK, Paxlovid is given to highly vulnerable people, such as those with cancer and weak immune systems. In the US, the eligibility criteria are broader, including anyone who is 65 or older or with conditions such as obesity or diabetes.
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In the past few weeks, some people are reported to have experienced viral “rebound” after coming off Paxlovid. This may be because SARS-CoV-2 hasn’t been eradicated from the body within the five days, so when some people stop taking Paxlovid, the amount of virus in their bodies increases again.
No deaths from this rebound have been reported, but doctors are warning that people experiencing it may be infectious.
Most of the drugs authorised to treat covid-19 have been used in those who develop a serious lung infection and need hospital treatment. By the end of 2021, a few medicines were available to help ward off severe illness and are given early in covid-19’s disease course.
While the various covid-19 drugs haven’t been directly compared in a trial, Paxlovid may be the most useful. The only other medicine that is a tablet and can be given early in the disease is molnupiravir, which is 30 per cent effective at preventing hospitalisations.
Paxlovid’s 88 per cent efficacy against hospitalisation and death comes from a 2021 trial, when the delta variant was dominant and none of the participants were vaccinated. Paxlovid may have less of an impact in 2022, now most people have had several vaccine doses and the omicron variant is dominant. Nevertheless, Paxlovid still seems to be “remarkably effective”, says at VA Boston Healthcare System.
On 13 May, , adding seven new incidences. Most of these people responded well to the drug initially and went on to test negative when using lateral flow tests, before relapsing around days nine to 12 of their illness, mostly with cold-like symptoms. In all eight cases, lateral flow tests returned to giving positive results, prompting some doctors to say the results must be wrong, says Charness.
All eight people recovered without treatment, but one of them passed covid-19 to two relatives. When three of the people had the virus infecting them sequenced, it showed that the rebound wasn’t due to the virus mutating to become Paxlovid resistant.
Rebounds could be occurring because “the immune system is not seeing [the virus] as much as it needs for a rapid response”, says Charness. “Nothing should change anybody’s inclination to take [Paxlovid] if they qualify, because it’s extremely effective against what can be a deadly illness. It’s just that in some people, there’s a round two.”
Earlier this month, Albert Bourla, CEO of Pfizer, told that people who rebound could take a second five-day Paxlovid course, “like you do with antibiotics”. But the US Food and Drug Administration (FDA) rebutted this in a “There is no evidence of benefit at this time for a longer course of treatment (e.g., 10 days rather than the 5 days recommended in the Provider Fact Sheet for Paxlovid) or repeating a treatment course of Paxlovid in patients with recurrent covid-19 symptoms .”
A reanalysis of Paxlovid’s trial data found that 1 to 2 per cent of the participants taking the medicine had seen an increase in viral load or their PCR tests returned to positive after their treatment finished, according to the FDA. But this also happened in the trial participants who got placebo tablets, so it is unclear if this rebound was related to Paxlovid specifically.
at Nottingham University Hospitals, UK, says his clinic knows of two people who seemed to experience a Paxlovid rebound, but more cases may have gone undiagnosed. “We don’t really know,” he says. “People might think it’s a [different] chest infection.”
Pfizer did not respond to a request for comment.
Article amended on 19 May 2022
This article has been amended to correct the vaccination status of participants in the 2021 Paxlovid trial.
