The results of two clinical trials – led by the Upstream Lab at St. Michael’s Hospital in Toronto and Oxford University, published in the New England Journal of Medicine – provide new evidence to consider when funding, prescribing, or taking Paxlovid to treat COVID-19.
The CanTreatCOVID study in Canada and the PANORAMIC study in the UK involved a total of over 4,200 people and found that Paxlovid does not reduce hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19, but it does help people recover a few days faster.
“In terms of the use of Paxlovid, guidelines across Canada have evolved from its initial approval through the CanTreatCOVID study to today. They have progressively narrowed and I think that this evidence will further refine them,” said Dr. Andrew Pinto, who led the Canadian trial. He is the Director of the Upstream Lab, based at MAP Centre for Urban Health Solutions, part of St. Michael’s Hospital (Unity Health Toronto). Upstream Lab Scientist Dr. Benita Hosseini was a Co-Principal Investigator of the CanTreatCOVID study.
In Ontario, the guidelines suggest that Paxlovid can be prescribed to treat mild-to-moderate COVID-19 in patients who are: 65 years of age and older, 18 years of age or older who are immunocompromised, or 18 to 64 years of age with at least one risk factor associated with more severe COVID-19 outcomes. For those not covered under the Ontario Public Drug Programs or private insurance, the cost could be about $1,400 out of pocket.
In January 2022, Health Canada authorized Paxlovid after initial study results revealed a reduced risk of hospitalization and death by nearly 90 per cent in unvaccinated high-risk patients. In contrast, the PANORAMIC trial and the CanTreatCOVID trial studied vaccinated patients.
“In today’s highly vaccinated populations, the benefits of Paxlovid have fundamentally changed,” said Oxford University’s Dr. Christopher Butler, 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 high-quality evidence for optimal, cost-effective targeting of this treatment.”
Paxlovid speeds recovery time in vaccinated patients
Both trials recruited vaccinated adults aged 50 and over, or younger adults with certain health conditions such as diabetes, heart disease, or a weakened immune system. All participants tested positive for COVID and had symptoms for five days or less. Almost everyone (about 98 per cent) had already received at least one dose of a COVID vaccine.
Interestingly, the studies revealed that Paxlovid did not reduce the chance of hospitalization or death from COVID-19 in those who were already vaccinated, but patients reported feeling better sooner and were more likely to stay recovered. In PANORAMIC, median recovery time was 14 days with Paxlovid compared to 21 days with usual care. CanTreatCOVID found recovery at 6 days versus 9 days.
TreatResp and PREPARED continue research to prepare for a future pandemic
CanTreatCOVID was one of the largest outpatient trials in Canada and has laid the groundwork for future research studies to be conducted in the community. It has been adapted into Upstream Lab’s new clinical trial called TreatResp, which launched in April 2026. TreatResp is designed to study treatments for respiratory infections, such as seasonal flu, and rapidly respond in the event of a future pandemic.
“For policymakers and funders, CanTreatCOVID demonstrates the value of having this type of research infrastructure ready to go so that we can study treatments for infections as they’re happening. In a new pandemic caused by a novel respiratory infection, our hope is TreatResp is fully up and running, and that it can be used to study treatments very quickly, both in terms of their efficacy and their cost-effectiveness,” said Dr. Pinto.
CanTreatCOVID was funded by the Canadian Institutes of Health Research (CIHR) and Health Canada, and supported by the Public Health Agency of Canada. CanTreatCOVID involved researchers from across Canada, including University of Toronto, McGill University, University of British Columbia, Simon Fraser University, University of Calgary, University of Manitoba, and Memorial University of Newfoundland.
Patients will be referred to TreatResp from another Upstream Lab research project called PREPARED, which is aimed at helping Canada prepare for future pandemics. Researchers are monitoring which viruses are circulating in our communities, by distributing free at-home test kits for COVID-19 and influenza to eligible patients in Ontario, Alberta, British Columbia and Newfoundland.
PREPARED is funded by the Canada Biomedical Research Fund. To learn more or to see if you’re eligible for a free at-home test kit, visit preparedcanada.org.
To read the full article:
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