Key messages

• In people with mild to moderate COVID-19 who are not admitted to hospital, molnupiravir probably makes little to no difference in reducing the risk of death compared with placebo (dummy treatment) or usual care. Molnupiravir may make little to no difference in reducing the need for hospitalisation or helping people get better faster. Molnupiravir probably does not increase the risk of unwanted effects, and does not increase the risk of serious unwanted effects.

• The evidence is unclear about whether molnupiravir is safe or effective in people who are admitted to hospital with COVID-19.

What is molnupiravir?

Molnupiravir is a pill used to treat COVID-19 in people who are at high risk of developing severe illness. It works by interfering with the ability of SARS‑CoV‑2 (the virus that causes COVID-19) to reproduce, helping the body to fight off the infection.

What did we want to find out?

We wanted to find out how molnupiravir compares to no treatment, placebo (dummy treatment), or standard of care in:

• decreasing death and hospitalisation in people with COVID-19;

• speeding up recovery (time to symptom resolution);

• clearing the virus that causes COVID-19 (viral clearance);

• safety, by looking at all unwanted events and serious unwanted events.

What did we do?

We searched for studies that evaluated molnupiravir compared with no treatment, placebo, or standard of care in people with confirmed COVID-19. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods. The types of studies we looked at were randomised controlled trials, which assign people randomly to two or more treatment groups. This is the best way to ensure that study groups are similar, and that investigators and participants don't know who is in which group.

What did we find?

The review included 11 studies with 31,272 participants, mostly outpatients (people not admitted to hospital) with mild to moderate COVID-19. When we combined results from studies that recruited outpatients (people not admitted to hospital) with mild to moderate COVID-19, we found the following key results:

• Molnupiravir probably results in little to no difference in the risk of death. Compared with people receiving placebo or standard of care, between four and 10 fewer people receiving molnupiravir will die within one month for every 10,000 people treated. We considered this reduction clinically insignificant.

• Molnupiravir may not reduce hospitalisations, meaning it may not prevent people from getting sicker or needing hospital care.

• There was evidence of increased viral clearance with molnupiravir by day 5, but this effect diminished by day 14, and we are not sure if it makes any real difference for patients.

• Molnupiravir may have little to no effect on the probability of having no symptoms by day 14 or day 28.

• Molnupiravir probably results in little to no difference in adverse events, and results in little to no difference in serious adverse events.

There are too few data to draw clear conclusions about molnupiravir's effects in people admitted to hospital with severe COVID-19.

What are the limitations of the evidence?

Most evidence comes from studies conducted in outpatients with mild to moderate COVID-19, so the results may not apply to people with severe illness who are hospitalised. The studies provided scarce evidence on long-term outcomes such as quality of life after recovery or how long the virus stays in the body. We were unable to analyse whether molnupiravir had a different effect in certain groups of people, like those with severe pre-existing conditions or people from low- or middle-income countries.

How up-to-date is the evidence?

The review includes studies published up to April 2024. Ongoing research could provide more insights in the future.