Paxlovid Speeds Recovery but Fails to Reduce Hospitalizations in Vaccinated COVID-19 Patients
Key Insights
Two major trials involving 4,232 participants found that Paxlovid does not reduce hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19 (search), despite helping them recover faster.
The UK PANORAMIC trial showed median recovery time of 14 days with Paxlovid versus 21 days with usual care, while the Canadian CanTreatCOVID trial found recovery at 6 days versus 9 days respectively.
Hospitalization rates remained very low in both trials, with no statistically significant differences between Paxlovid and usual care groups across either study.
Paxlovid (nirmatrelvir-ritonavir (search)) does not reduce hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19 (search), despite helping them recover faster, according to results from two national trials published in the New England Journal of Medicine. The findings from 4,232 participants across the UK PANORAMIC trial and Canadian CanTreatCOVID trial help clarify who should receive Paxlovid now that widespread vaccination has dramatically reduced the risk of severe outcomes.
Trial Design and Participants
The UK PANORAMIC trial, funded by the National Institute for Health and Care Research (search) (NIHR) and led from the University of Oxford, enrolled 3,516 participants with COVID-19 (search) across its Paxlovid arm from April 2022 to March 2024. The Canadian CanTreatCOVID trial, led by Dr. Andrew Pinto, director of Upstream Lab (Unity Health Toronto), enrolled 716 participants from January 2023 to September 2024.
Both trials recruited adults aged 50 or over, or younger adults with additional conditions such as diabetes (search) or asthma (search). Over 98% of all participants were vaccinated, representing a population very different from the one in which Paxlovid was originally studied.
Faster Recovery Without Reduced Severe Outcomes
Participants taking Paxlovid recovered substantially sooner than those receiving usual care. 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, respectively, though it measured recovery using slightly different criteria. Paxlovid also significantly reduced viral load by day 5, which may have implications for reduced opportunity for spread.
However, very few participants in either trial were hospitalized within 28 days. 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.
Safety Profile Consistent with Known Effects
The safety profile matched what is already known about Paxlovid. In PANORAMIC, 90.4% reported at least one side effect – predominantly altered taste (dysgeusia) and gastrointestinal symptoms typical for this drug – with around 8% discontinuing treatment because of side effects. Serious adverse events remained rare in both groups.
Clinical and Policy Implications
"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 hospitalizations or deaths. This provides essential evidence for optimal, cost-effective targeting of this treatment."
Paxlovid was approved in 2021 based on trials showing an 88% reduction in hospitalization or death among unvaccinated high-risk adults. 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.
These findings apply specifically to higher-risk vaccinated adults (aged 50 or over, or aged 18 or over with comorbidities such as diabetes (search) or chronic lung disease). They do not change recommendations for the highest-risk immunocompromised patients, for whom Paxlovid remains first-line treatment under current NICE guidance.
Research Infrastructure and Future Preparedness
The trials demonstrated innovative approaches to clinical research during the pandemic. The UK PANORAMIC trial pioneered remote participation methods – online consent, medication dispatched through its in-house dispensing facility, and self-collected samples – removing many traditional barriers to taking part and thus 'democratising trials research.'
"These trials demonstrate precisely what evidence-based policy and medical care should look like – rigorously testing treatments as conditions change," said Professor Jonathan Van-Tam, former UK Deputy Chief Medical Officer and Co-investigator, University of Nottingham. "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."
Oxford's Primary Care Clinical Trials Unit and Toronto's Upstream Lab are now applying these methods to trials of other respiratory infections through the ECRAID-Prime and TreatResp trials – carrying forward the research infrastructure developed during the pandemic to benefit broader public health and prepare for future outbreaks.