COVID antiviral drug Paxlovid speeds recovery but doesn't reduce hospitalization in vaccinated patients, trials find

Major UK and Canadian studies provide crucial evidence for targeting use of Paxlovid in today's highly vaccinated populations

Paxlovid (nirmatrelvir-ritonavir) does not reduce hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19, according to results from two national trials published in the New England Journal of Medicine.

The findings from 4,232 participants provide crucial evidence for targeting Paxlovid to those who may benefit most, now that widespread vaccination has dramatically reduced population-level risk of severe outcomes.

In Canada, the CanTreatCOVID trial, led by Dr. Andrew Pinto, director of the Upstream Lab (MAP Centre for Urban Health Solutions, St. Michael’s Hospital, Unity Health Toronto), in collaboration with Dr. Todd Lee and Dr. Emily McDonald at the Research Institute of the McGill University Health Centre (The Institute), enrolled 716 participants from January 2023 to September 2024. CanTreatCOVID was funded by the Canadian Institutes of Health Research (CIHR) and Health Canada and was supported by the Public Health Agency of Canada.

In the UK, the PANORAMIC trial, funded by the National Institute of Health and Care Research (NIHR) and led from the University of Oxford, enrolled 3,516 participants (December 2021–March 2024).

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.

Faster recovery with known safety profile

Although there was no difference in hospitalization, participants taking Paxlovid reported feeling better substantially sooner. In PANORAMIC, median recovery time was 14 days with Paxlovid compared to 21 days with usual care. Using slightly different assessment criteria and with the trial conducted later in the pandemic, CanTreatCOVID reported a shorter recovery time of 6 days compared to 9 days.  While patients knew which treatment they were assigned to, viral load was also significantly reduced by day 5 of treatment.

Safety findings were consistent with Paxlovid's known side-effect profile. In PANORAMIC, 90.4% reported at least one side effect – predominantly altered taste (dysgeusia) and gastrointestinal symptoms typical for this drug – with 14% discontinuing early. Serious adverse events remained rare in both groups.

Paxlovid was approved in the UK in 2021 based on a randomized trial showing an 88% reduction in hospitalization or death among unvaccinated high-risk adults, and its use was restricted in May 2025 to 'highest-risk' patients (e.g., transplant recipients, severe liver disease), due to cost-effectiveness concerns. In Canada, it was authorized by Health Canada in January 2022 and every province has its own criteria for funding Paxlovid. 

"In today's highly vaccinated populations exposed to the Omicron variant, the benefits of Paxlovid have fundamentally changed," says Professor Christopher Butler, Nuffield Department of Primary Care Health Sciences, University of Oxford, who led the UK trial. "While people feel better sooner, we found no reduction in the already low rate of hospitalizations or deaths. This provides essential evidence for optimal, cost-effective targeting of this treatment."

“This was an important trial to conduct. This more modern evidence helps us understand the potential role of anti-viral therapy in COVID-19 in the era where people have been vaccinated or have natural immunity. As the times change, treatment decisions must adapt. This joint publication proves that independent trials using similar protocols can generate robust evidence collaboratively,” says Dr. Todd Lee, a co-principal investigator on CanTreatCOVID and a scientist in the Infectious Diseases and Immunity in Global Health (IDIGH) Program at The Institute.

“This publication highlights how PANORAMIC and CanTreatCOVID pioneered innovative remote participation approaches—such as online consent, couriered medications, and self-collected samples—to make clinical trials more accessible to patients. At The Institute, we were early leaders in this area, working to develop approaches that now provide valuable tools to evaluate new treatments quickly and effectively in future health emergencies,” says Dr. Emily McDonald, also a co-principal investigator on CanTreatCOVID and a scientist in the IDIGH Program at The Institute.

Very low hospitalization rates, no significant difference

Hospitalization or death at 28 days was very rare. In PANORAMIC, rates were 0.8% with Paxlovid versus 0.7% with usual care. In CanTreatCOVID, rates were 0.6% versus 1.2%. Neither study found a statistically significant difference. There were no deaths in either trial during the Paxlovid recruitment period.

Trials in real-world settings

In Canada, CanTreatCOVID was created to determine which medications can prevent people from being hospitalized, help people with COVID-19 feel better more quickly, and prevent the long-term effects of COVID-19. It was open to participants from Ontario, Québec, British Columbia, Alberta, Manitoba, or Newfoundland and Labrador, thanks to collaborations with researchers from across Canada, including University of Toronto, University of British Columbia, University of Calgary, University of Manitoba, McGill University, Memorial University of Newfoundland, and Simon Fraser University. Both Dr. Lee and Dr. McDonald were on the trial steering committee that coordinated the study in Canada and led recruitment in Québec.

"This is a demonstration of public funding for studies to rigorously test treatments for infections like COVID and we’re excited to continue with TreatResp to be ready ahead of a future pandemic," said Dr. Pinto from the Upstream Lab. 

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 research partners in Scotland, Wales and Northern Ireland. The trial recruited nearly 30,000 participants across multiple treatments, demonstrating the UK's world-leading capacity for rapid, large-scale evidence generation through academic-NHS, industry, and community partnerships.

About the study

Butler, C.C., Pinto A.D., et al. Oral nirmatrelvir-ritonavir for COVID-19 in higher risk outpatients. N Engl J Med 2026;394:1583-94. DOI: 10.1056/NEJMoa2502457