COVID antiviral speeds recovery, but doesn’t reduce hospitalization in vaccinated patients

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

The COVID antiviral drug Paxlovid (nirmatrelvir-ritonavir) can help people recover faster, but does not reduce hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19, according to new results from two clinical trials.

The findings, published in the New England Journal of Medicine, provide crucial evidence for targeting Paxlovid to those who will benefit most, particularly as widespread vaccination has dramatically reduced the risk of severe outcomes.

“This study underscores the importance of continuously evaluating treatments in the context of an evolving pandemic,” said co-investigator Dr. Srinivas Murthy, clinical associate professor of pediatrics at the UBC Faculty of Medicine and investigator at BC Children’s Hospital Research Institute. “As population immunity changes, so too must our approach to care. In the future, embedding clinical trials into public health responses will be key to identifying the most effective therapies.”

Dr. Srinivas Murthy

The findings stem from two national clinical trials involving more than 4,200 participants. Dr. Murthy was the lead B.C. investigator on the Canadian CanTreatCOVID trial led out of St. Michael’s Hospital in Toronto, while the UK PANORAMIC trial was led from the University of Oxford.

Both trials recruited adults aged 50 or over, or younger adults with additional conditions such as diabetes or asthma. Over 98 per cent of all participants were vaccinated.

By testing the drug in mostly vaccinated higher-risk patients, the trials reflect today’s changed pandemic landscape.

“In today’s highly vaccinated populations exposed to the Omicron variant, the benefits of Paxlovid have fundamentally changed,” said Dr. Christopher Butler, a professor at the 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.”

Faster recovery in vaccinated patients

Paxlovid was approved in the UK in 2021 based on trials showing an 88 per cent reduction in hospitalization or death among unvaccinated high-risk adults. Health Canada similarly authorized Paxlovid in January 2022.

Interestingly, the new 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.

“These trials demonstrate precisely what evidence-based policy and medical care should look like – rigorously testing treatments in the populations they are intended for, as conditions change,” said co-investigator Dr. Jonathan Van-Tam, former UK Deputy Chief Medical Officer and professor at the University of Nottingham.

International collaboration for pandemic preparedness

The joint publication demonstrates how independent trials using similar protocols can deliver robust findings more quickly than multiple small studies. Both CanTreatCOVID and PANORAMIC pioneered innovative remote participation methods — including online consent, couriered medication and self-collected samples — that removed traditional barriers to trial access.

The researchers say the studies highlight how pandemic-era research infrastructure and approaches can be adapted to strengthen broader public health systems beyond COVID-19.

“Treatment decisions must evolve as the pandemic landscape changes,” said Dr. Butler. “The research infrastructure and methods developed through these trials provide a model for rapidly evaluating treatments during future health emergencies.”

A version of this story was originally published on the Oxford University website. CanTreatCOVID was funded by the Canadian Institutes of Health Research (CIHR) and Health Canada, and supported by the Public Health Agency of Canada. PANORAMIC was funded by the funded by the National Institute of Health and Care Research.