Paxlovid (nirmatrelvir-ritonavir) does not reduce hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19, despite helping them recover faster, according to results from two national trials published today in the New England Journal of Medicine. With COVID-19 still causing significant illness and death, clinicians urgently need to know which patients benefit most from early antiviral treatment.
The findings, from 4,232 participants across the two trials, help clarify who should receive Paxlovid now that widespread vaccination has dramatically reduced the risk of severe outcomes.
The UK PANORAMIC trial, funded by the National Institute for Health and Care Research (NIHR) and led from the University of Oxford, enrolled 3,516 participants with COVID-19 across its Paxlovid arm (April 2022–March 2024). The Canadian CanTreatCOVID trial, led by Dr Andrew Pinto, director of Upstream Lab (Unity Health Toronto), enrolled 716 participants (January 2023–September 2024).
Paxlovid was approved in 2021 based on trials showing an 88% reduction in hospitalisation or death among unvaccinated high-risk adults. The two new trials tested the drug in mostly vaccinated higher-risk patients – a population very different from the one in which Paxlovid was originally studied. In May 2025, the National Institute for Health and Care Excellence (NICE) restricted routine NHS use to a narrower 'highest-risk' cohort (e.g. transplant recipients, severe liver disease), citing cost-effectiveness concerns.
"In today's highly vaccinated populations, the benefits of Paxlovid have fundamentally changed," said Professor Christopher Butler, Nuffield Department of Primary Care Health Sciences, University of Oxford, who led the UK trial. "While people feel better sooner from treatment with this important antiviral drug, we found no reduction in the already low rate of hospitalisations or deaths. This provides essential evidence for optimal, cost-effective targeting of this treatment."
Read the full story on the Nuffield Department of Primary Care Health Sciences website.