COVID-19 antiviral drug speeds recovery but does not cut risk of hospitalisation

Large trials in the UK have found that nirmatrelvir–ritonavir accelerates recovery from COVID-19 but it does not reduce hospitalisation or death in vaccinated higher-risk populations

Paxlovid, the oral antiviral combination of nirmatrelvir and ritonavir, has not reduced hospital admissions or deaths in vaccinated adults at higher risk of severe COVID-19, although it has shortened recovery time, according to findings from two national trials in the UK. The results address a pressing clinical question as the pandemic enters a phase characterised by widespread vaccination and lower baseline risk of severe outcomes.

The combined evidence, drawn from 4,232 participants, has clarified which patient groups are most likely to benefit from early antiviral therapy. Investigators conducted the UK PANORAMIC trial, funded by the UK’s National Institute for Health and Care Research and led by the University of Oxford, alongside the Canadian CanTreatCOVID trial, which was led by Dr. Andrew Pinto of Upstream Lab at Unity Health Toronto.

The PANORAMIC study enrolled 3,516 participants between April 2022 and March 2024, while CanTreatCOVID recruited 716 participants from January 2023 to September 2024. Both trials focused on adults aged 50 years or older, or younger individuals with comorbidities including diabetes or asthma. More than 98 per cent of participants had received a COVID-19 vaccination, a factor that distinguishes these cohorts from those in earlier pivotal studies.

Paxlovid received regulatory approval in 2021 after trials demonstrated an 88 per cent reduction in hospitalisation or death among unvaccinated high-risk individuals. However, the current trials have evaluated its effectiveness in a substantially different population and epidemiological landscape. In May 2025, the National Institute for Health and Care Excellence restricted routine National Health Service (NHS) use of Paxlovid to a narrower group defined as at highest risk, including transplant recipients and patients with severe liver disease, under cost-effectiveness considerations.

“In today's highly vaccinated populations, the benefits of Paxlovid have fundamentally changed,” said Dr. Christopher Butler of the Nuffield Department of Primary Care Health Sciences at the University of Oxford, who led the PANORAMIC trial.

“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,” he said.

The PANORAMIC trial has operated through the University of Oxford’s Primary Care Clinical Trials Unit in collaboration with national research networks across the UK, including Health and Care Research Wales, NHS Research Scotland and the Health and Social Care Board in Northern Ireland. Across multiple treatment arms, the platform has recruited more than 29,000 participants, making it one of the largest community-based COVID-19 trials conducted.

Investigators have also introduced remote participation methods, including online consent, centralised medication dispatch and self-collection of samples, which have reduced logistical barriers and expanded access to clinical research. This approach has enabled broader representation and has established a framework for future large-scale pragmatic trials.

Both studies have demonstrated that Paxlovid accelerates recovery. In PANORAMIC, median recovery time was 14 days in the treatment group compared with 21 days under usual care. In CanTreatCOVID, recovery occurred at six days compared with nine days, although the definition of recovery differed slightly between trials. The antiviral has also reduced viral load by day five, a finding that may have implications for onward transmission.

The safety profile has remained consistent with prior evidence. In the PANORAMIC cohort, 90.4 per cent of participants reported at least one adverse effect, most commonly dysgeusia and gastrointestinal symptoms, with approximately 8 per cent discontinuing treatment as a result. Serious adverse events were rare across both studies.

“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 deputy chief medical officer for the UK government and co-investigator at the 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 National Institute for Health and Care Research – capabilities that are critical for future pandemic preparedness,” he said.

Rates of hospitalisation within 28 days were low in both trials. In PANORAMIC, 0.8 per cent of participants who received Paxlovid required hospital care compared with 0.7 per cent in the usual care group. In CanTreatCOVID, rates were 0.6 per cent and 1.2 per cent respectively. Neither trial identified a statistically significant difference, and no deaths occurred during the recruitment periods.

The joint publication has illustrated the value of parallel independent trials that use harmonised protocols to produce robust and generalisable findings. Such coordination has strengthened confidence in the conclusion that Paxlovid does not confer additional protection against severe outcomes in vaccinated higher-risk populations.

Researchers are now applying similar methodologies to other respiratory infections through initiatives including ECRAID-Prime and TreatResp, with the aim to translate pandemic-era infrastructure into long-term public health capability.

“These results demonstrate the value of rapid, large-scale evidence generation through NHS partnerships,” said Dr. Phil Evans, national associate director of health and care in the National Institute for Health and Care Research Delivery Network.

“The UK's research infrastructure, built through the National Institute for Health and Care Research, and academic clinical trials units allowed us to generate this evidence quickly.”

The findings apply specifically to vaccinated higher-risk adults and do not alter current guidance for individuals with severe immunocompromise, for whom Paxlovid remains first-line therapy under existing recommendations. Clinical guidance continues to emphasise the need to initiate treatment as soon as possible after symptom onset.

“Treatment decisions must evolve as the pandemic landscape changes,” said Professor Butler.

“The research infrastructure and methods developed through these trials provide a model for rapidly evaluate treatments during winter epidemics and future health emergencies,” he concluded.

For further reading please visit: Oral nirmatrelvir-ritonavir for COVID-19 in higher risk outpatients