How Molnupiravir Affects COVID-19 Recovery Time, Risk of Hospitalization and Death

Previous studies have suggested the oral antiviral medication molnupiravir effectively reduces hospitalizations in patients with mild-to-moderate COVID-19. However, this is contradicted by recent findings from a randomized controlled trial.

The study, published in The Lancet, found that a molnupiravir regimen did not decrease the risk of hospitalization or death in vaccinated adults with a high risk of COVID-19 morbidity and mortality.

The investigators specifically wanted to study how molnupiravir affects vaccinated persons at an increased risk of morbidity and mortality, as the safety, efficacy, and cost-effectiveness of the oral antiviral has not been established in this patient population.

Additionally, if vaccinated patients do not benefit from molnupiravir, it could hinder antimicrobial stewardship efforts to continue giving them the treatment.

“While it’s critical to ensure that patients who are likely to benefit treatment with antiviral treatments, such as molnupiravir, receive them; using antivirals to treat patients who are unlikely to benefits carries the risk of further driving antimicrobial resistance, wasting resources, and exposing people to unnecessary harm,” explained study co-author Ly-Mee Yu, DPhil, a professor at the University of Oxford.

PANORAMIC, the UK-based, national, multicenter, open-label, multigroup, randomized controlled trial sought to determine whether adding molnupiravir to standard-of-care reduced COVID-19 hospitalizations and deaths in a high-risk vaccinated population.

The study included adult participants 50 years and older, or 18 and older if they had relevant comorbidities increasing their risk of severe or fatal COVID-19; the average participant age was 57 years. All participants had been infected with COVID-19 for no more than 5 days.

The 25708 trial participants were randomly assigned 1:1 to receive either 800 mg molnupiravir twice daily for 5 days and usual care, or usual care only. Before randomization, participants were stratified by age and vaccination status.

The primary study outcome was all-cause hospitalization or death within 28 days of treatment randomization. Secondary outcomes were related to recovery time and infection symptoms, which patients reported daily via an online diary for 28 days of follow-up.

There was no benefit observed in reducing hospitalization and death rates between the molnupiravir group and the standard care group. The former group had 105 cases (0.8%) of hospitalization or death, while the latter control group had 98 cases (0.8%) of hospitalization or death.

However, the molnupiravir cohort did report more favorable secondary outcomes. Their average length of COVID-19 infection was 9 days, compared to an average 15-day infection observed in the control group.

“Although this trial found no benefit from molnupiravir treatment on its primary outcome—which hypothesized that treatment with molnupiravir for vaccinated, at-risk patients would reduce the likelihood of hospitalization or death—the trial suggests that this treatment could have other benefits when being used to treat COVID-19, such as a faster recovery time and reduced follow up with health services,” said study lead author Christopher C. Butler, MD, a professor at the University of Oxford.