COVID antiviral speeds recovery but doesn't reduce hospitalisation in vaccinated patients
23 April 2026
Antiviral drug 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 in the New England Journal of Medicine, new research spanning over 4000 patients from Canada and the UK helps clarify who should receive Paxlovid now that widespread vaccination has dramatically reduced the risk of severe outcomes.
With COVID-19 still killing more than 100 people and hospitalising over 1,000 each week in the UK, clinicians urgently need to know which patients benefit most from early antiviral treatment.
Paxlovid was approved in 2021 based on trials showing an 88% reduction in hospitalisation or death among unvaccinated high-risk adults, but its effectiveness was not clear in vaccinated high-risk patients.
The UK PANORAMIC trial, funded by the National Institute for Health and Care Research (NIHR) and led by the University of Oxford, enrolled 3,516 participants for the Paxlovid evaluation with Covid-19 between December 2021 and March 2024. The Canadian CanTreatCOVID trial, led by Dr Andrew Pinto, director of Upstream Lab at Unity Health Toronto, enrolled 716 participants between January 2023 and September 2024.
Although the pandemic feels far away, in spite of vaccination, acquired immunity, and viral evolution, some patients - particularly those at high risk - continue to be seriously ill and admitted to hospital with Covid-19 infection.
Professor Kerenza Hood, Dean of Research & Innovation, College of Biomedical and Life Sciences at Cardiff University and Welsh lead for the PANORAMIC Trial, said: “Early treatment with direct-acting antiviral drugs could prevent deterioration in their condition, reduce the risk of hospital admission, and speed up recovery. By testing whether we can apply current knowledge to vaccinated high-risk patients, we can enrich our understanding of how we can prevent hospitalisation with Covid-19 in high-risk patients even when they are vaccinated.”
Both trials recruited adults aged 50 or over, or younger adults with additional conditions such as diabetes or asthma. Over 98% of all participants were vaccinated.
The study found that participants taking Paxlovid recovered substantially sooner, and Paxlovid also significantly reduced viral load by day 5.
In today's highly vaccinated populations, the benefits of Paxlovid have fundamentally changed.
Professor Christopher Butler, Nuffield Department of Primary Care Health Sciences at the University of Oxford, who led the UK trial, said: “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."
During the study, very few participants were hospitalised or died within 28 days and there were no deaths in either trial during the Paxlovid recruitment period.
Professor Jonathan Van-Tam, former UK Deputy Chief Medical Officer and Co-investigator, University of Nottingham, said: "These trials demonstrate precisely what evidence-based policy and medical care should look like – rigorously testing treatments as conditions change.
"The UK led the world in COVID treatment trials because we have unified health systems, strong academic trial units, and standing research infrastructure through the NIHR – capabilities that are critical for future pandemic preparedness."
Professor Phil Evans, National Associate Director of Health and Care in the NIHR Research Delivery Network, added: "These results demonstrate the value of rapid, large-scale evidence generation through NHS partnerships. The UK's research infrastructure, built through the NIHR, and academic clinical trials units allowed us to generate this evidence quickly."
The UK PANORAMIC trial was designed, coordinated and led by the University of Oxford's Primary Care Clinical Trials Unit, working with the NIHR Research Delivery Network across England and by Health and Care Research Wales, NHS Research Scotland, the Health and Social Care Board in Northern Ireland.
The research, Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients, was published in New England Journal of Medicine.
