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COVID rebound is surprisingly widespread — even with out Paxlovid

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Health workers perform a Covid-19 swab test on a resident in the Xuhui district of Shanghai, China, on July 7, 2022.

A well being care employee swabs an individual in Shanghai, China, for SARS-CoV-2.Credit score: Qilai Shen/Bloomberg by way of Getty

After the game-changing COVID-19 antiviral Paxlovid started for use in late 2021, researchers observed a perplexing pattern. In some folks taking the drug, signs and detectable virus vanish, solely to mysteriously return days later.

After months of greedy at straws, scientists are starting to make some headway in understanding ‘Paxlovid rebound’. Two current research recommend that it’s surprisingly widespread for SARS-CoV-2 to return in untreated instances of COVID-191, whereas hinting that the virus’s comeback is fiercer and extra widespread in individuals who take Paxlovid2.

“We’re all seeing people who find themselves taking Paxlovid doing rather well after which all of the sudden they’re getting sick once more,” says Michael Charness, a physician-scientist at VA Boston Healthcare in Massachusetts, who revealed an early description of Paxlovid rebound3. “There are such a lot of unanswered questions.”

Viral resurgence

Paxlovid ― a mixture of the oral antiviral medicine nirmatrelvir and ritonavir ― has been a boon in nations the place it’s broadly accessible. A medical trial sponsored by the producer Pfizer, headquartered in New York Metropolis, confirmed that it decreased the chance of hospitalization and demise in at-risk unvaccinated people4. Actual-world research recommend the remedy’s advantages might additionally lengthen to vaccinated folks5.

The Pfizer trial workforce observed instances of rebound each in individuals who bought Paxlovid and in those that took a placebo4. However full particulars of those instances usually are not accessible, scientists say.

To find out the frequency of rebound within the absence of Paxlovid remedy, Jonathan Li, a physician-scientist at Brigham and Ladies’s Hospital in Boston, Massachusetts, and his workforce analysed information from a whole lot of people that had been randomized to obtain a placebo in a large-scale trial of COVID-19 antibody medicine.

Multiple-quarter of members who had been contaminated with SARS-CoV-2 reported a rebound of their signs, whereas 1 in 8 noticed the virus return to excessive ranges1. But, simply 1–2% of individuals had each options of rebound. The research was posted to the medRxiv preprint server on 2 August and has not but been peer reviewed.

Covid comeback: People who receive the antiviral Paxlovid can experience a rebound in symptoms and viral levels.

Supply: Ref 1.

Li says that this means that the rebound of SARS-CoV-2 not often causes signs, and that signs’ reappearance might stem as an alternative from elements aside from viral resurgence, akin to lingering immune responses or one other an infection altogether. “The primary take-home message is that restoration from COVID-19 isn’t going to be a linear course of”, Li says.

Li’s workforce, in addition to many others, are actually finding out individuals who take Paxlovid each earlier than and after rebound tends to happen. One such research discovered indicators that Paxlovid rebound is completely different to the resurgences that happen with out remedy2. The research, posted to medRxiv on 4 August, has not but been peer reviewed.

The research, led by infectious-disease doctor and vaccine scientist Kathryn Stephenson at Beth Israel Deaconess Medical Middle in Boston, intently adopted 11 individuals who took Paxlovid for COVID-19 and 25 who didn’t. Multiple-quarter of the Paxlovid recipients rebounded, based mostly on ranges of SARS-CoV-2, in contrast with simply one of many 25 untreated folks. Furthermore, folks with Paxlovid rebound had excessive ranges of virus for a number of days, as if they’d new acute infections. “The only case of viral rebound with out remedy was extra like a viral ‘blip’,” Stephenson wrote on Twitter.

Charness says that Paxlovid rebound does appear to be qualitatively completely different from rebound in untreated folks, whose viral ranges not often reached the peaks of their preliminary an infection.

However the reason for Paxlovid rebound stays unclear. Research have advised that it’s unlikely to be as a result of viral drug resistance or feeble immune responses in rebounders. Researchers are testing whether or not viral replication, having been suppressed by Paxlovid, can bounce again when the drug vanishes from the physique, resulting in excessive viral ranges and potent immune responses that may trigger signs to reappear.

Physicians additionally want a greater information as to find out how to deal with, and in the end stop, Paxlovid rebound. Mark Siedner, a medical epidemiologist at Massachusetts Common Hospital in Boston who’s finding out Paxlovid rebound, says the phenomenon reminds him of what happens when different ailments are handled for too brief a time. “This smells like remedy length isn’t lengthy sufficient for the subgroup of people that have rebound.”

The drug is presently given for 5 days, however Charness says it’s price taking a look at longer remedy intervals — so long as this doesn’t promote drug resistance. “There may be nonetheless lots to study.”

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