Trial finds molnupiravir does not reduce COVID-19 hospitalisation or deaths in vaccinated people at high risk

Researchers have today (22 December 2022) released findings from a clinical trial investigating the effectiveness of the antiviral treatment molnupiravir against COVID-19 – the first treatment tested in the ongoing PANORAMIC trial.

In their paper published in The Lancet, they reported that molnupiravir did not reduce hospitalisations or deaths among higher risk, vaccinated adults with COVID-19 in the community. The treatment was, however, associated with a faster recovery time and reduced viral detection and load – participants who received molnupiravir reported feeling better compared to those who received usual care.

Molnupiravir (brand name Lagevrio) was the first treatment to be studied by the Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community (PANORAMIC), set up to identify which groups of higher risk people were most likely to benefit from new antiviral treatments for COVID-19. The study allows multiple antiviral drugs to be tested in parallel.

Chris Butler, Professor of Primary Care in the University of Oxford’s Nuffield Department of Primary Care Health Sciences and co-Chief Investigator of PANORAMIC, said: “Finding effective, safe and scalable early treatments for COVID-19 in the community is the next major frontier in our research response to the ongoing worldwide pandemic. It is in the community where treatments could have a massive reach and impact. But decisions about who to treat should always be based on evidence from rigorous clinical trials that involve people who would most likely be prescribed the drugs.

“The evidence PANORAMIC has produced about molnupiravir will guide treatment decisions for COVID-19 world-wide. It is rapidly generating critically important clinical evidence from within the pandemic to guide care during the pandemic itself, in this case determining effects of molnupiravir among people who are almost all vaccinated.

“We must not forget the other ongoing pandemic of antibiotic resistance, which in part stems from using antimicrobial drugs at scale before we did rigorous clinical trials to find out who really benefits form treatment, and who does not. The PANORAMIC team is also doing the necessary trials and gathering evidence about these treatments before we go straight to widespread use.

Study participants were within five days of symptoms onset and either aged over 50 years in good health or between 18-50 with underlying health conditions that made them clinically more vulnerable. A total of 25,786 study participants were randomly assigned to receive either molnupiravir or the usual standard of NHS care.

50 (0·4%) participants experienced serious adverse events in the molnupiravir group and 45 (0·4%) in usual care.

Patients in a sub-group treated with molnupiravir showed reduced viral detection and viral load on Day 7.

Recruitment of people from ethnically and culturally diverse backgrounds into clinical trials has been important in ensuring audiences likely to benefit from treatment are represented.

The University of Liverpool’s Professor Saye Khoo, said: “Antivirals can save lives; the challenge is to identify which drugs are effective in a constantly changing environment where clinical disease and viral variants are evolving. The UK’s comprehensive programme of antiviral research spans early phase trials (such as AGILE) to full efficacy evaluations in PANORAMIC, and Liverpool is proud to work with colleagues in Oxford and across the UK so that together we can find the best treatments for COVID-19.”

Paul Little, Professor of Primary Care Research at the University of Southampton and co-Chief Investigator of PANORAMIC, said: “PANORAMIC is one of the most remarkable studies to have come from primary care, not only in highly innovative recruitment methods during an ongoing pandemic, but in providing timely, clear evidence for patients, their doctors and policy makers for a new antiviral drug – demonstrating that molnupiravir is effective in reducing viral load and helping symptoms, but with no benefit in reducing hospital admissions in a largely vaccinated population.”

Professor Sir Jonathan Van-Tam, Pro-Vice-Chancellor for the Faculty of Medicine and Health Sciences at the University of Nottingham and study co-author, said: “While molnupiravir was originally found to work well to reduce hospitalisation in patients with Covid, these were unvaccinated patients.

“This latest research has repeated the exercise in the highly vaccinated population, demonstrating that the vaccine protection is so strong that there is no obvious benefit from the drug in terms of further reducing hospitalisation and deaths.

“However, symptom duration and virus shedding are both markedly reduced, and we have to wait much longer to know if there will be any discernible effects on long COVID.

“This study is an excellent example of why large-scale, rigorous, prospective trials like this are so essential in assessing the effectiveness of drugs to ensure that they are only used in patients where there will be a tangible benefit to their care.”

PANORAMIC is led by the University of Oxford and funded by UK Research and Innovation (UKRI) and National Institute for Health and Care Research (NIHR).

The study will now continue to investigate new antiviral medications such as Paxlovid. For more information or to enrol, please visit

Click here to see the full research paper.