One of the pricier antiviral treatments for COVID-19, costing about $700 for a seven-day course in the US (compared to about $530 for a five-day course of Paxlovid), has failed to show better outcomes for severe, hospitalized patients.

According to the findings of a randomised controlled trial, which were published in The Lancet journal, molnupiravir (taken as an 800mg dose twice daily for five days) does not lower hospital admissions or deaths in adults who have received vaccinations and have COVID-19 infection and are at higher risk of death. However, compared to the control group, the patients receiving molnupiravir treatment at home recovered more quickly.

Studies have shown that molnupiravir can help people with mild to moderate COVID-19 stay out of the hospital longer, and the WHO recommends it for people who are most likely to end up in the hospital. However, research has only been done so far in mainly uninfected groups and before the omicron variant appeared. This new experiment was conducted in a largely immunized community where the majority of COVID-19 infections were the omicron variant, making it more relevant to the situation in the UK at the moment.

The cost of a seven-day treatment of molnupiravir, one of the most costly antivirals used to treat COVID-19, is close to $700 in the United States, (compared to close to $530 for a five-day course of Paxlovid). Molnuvirapir was delivered to study participants and administered orally at home.

Although this trial did not demonstrate a benefit from molnupiravir treatment on its primary outcome, which was the reduction in hospitalization or death for vaccinated, at-risk patients, the trial suggests that this treatment may have other advantages when used to treat COVID-19, such as a quicker recovery and less follow-up with healthcare providers,” according to the authors. 

“This could help to ease the burden on UK health services through the treatment of selected patients at home, during times of high disease burden and pressure on key services,” adds lead author Professor Chris Butlet.

The research recruited 25,708 UK health center patients over 18 (average age 57) at increased risk of COVID-19-related mortality or hospitalization. Patients aged 50 and over, or those aged 18 and up with significant underlying health issues, were deemed to be at increased risk of hospitalization or death. Patients had a confirmed case of omicron COVID-19 infection and had been experiencing symptoms for no more than five days prior to starting therapy. The results show what happened to patients who were treated between December 8, 2021, and April 27, 2022, when the omicron wave was at its strongest in the UK.

About half of the 12,774 people in the trial were given 800 mg of molnupiravir twice a day at home for five days, in addition to the standard care. 12,934 participants in the control group got routine treatment.

The primary purpose of the study was to determine whether molnupiravir lowered the risk of hospitalization or death. Symptoms and recovery time are secondary goals (specified outcome measures that are not as essential as the main outcome measure but are nevertheless interesting in assessing the effectiveness of an intervention. During the 28-day follow-up, patients recorded their outcomes using an online diary.

There was no difference in hospitalization or mortality rates between the molnupiravir and control groups. 105 instances of hospitalization or death (0.8%) occurred in the group receiving molnupiravir treatment, compared to 98 cases (0.8%) in the control group.

Participants who took molnupiravir saw better results for a number of the study’s secondary endpoints. Patients who took molnupiravir had sickness for an average of nine days as opposed to 15 days in the control group. Using statistical modeling that took into account how long it took people in both groups to get better, the authors found that people who took molnupiravir got better on average 4.2 days faster than people in the control group.

Seven patients in the control group also did not improve over the 28-day observation period. After the trial, 20% of the people who were treated with molnupiravir went to see their doctor again, while 24% of the people in the control group did the same.

As countries continue to implement their plans for controlling COVID-19 infections, the problem of antibiotic resistance must not be overlooked, the authors point out. 

While it’s important to make sure that patients who will benefit from antiviral medications like molnuvirapir get them, utilizing antivirals to treat patients who won’t benefit from them runs the risk of promoting antimicrobial resistance, wasting resources, and causing unneeded damage to individuals. 

So, Professor Ly-Mee Yu of the University of Oxford in the UK, a study co-author, says that their research “contributes to the valuable evidence base on who should not be treated with these precious, newly discovered agents, to empower clinicians to make decisions led by robust evidence when prescribing treatments for COVID-19 infections.”

The advantages of using molnupiravir must be weighed against the cost-effectiveness and impact on healthcare systems, the authors warn. Long-term effects of molnupiravir therapy for COVID-19 are currently being assessed, and more health and economic assessments are being conducted on a continuous basis. The authors also admit that the open-label design of the trial meant they couldn’t figure out how well molnupiravir helped with symptoms caused by the placebo effect. But this limitation is not likely to change the trial’s main measure of success, which is the number of people who were hospitalized or died.

Professor Michael Kidd from the Australian Government Department of Health and Aged Care says that these “findings might be “less applicable” in people with COVID-19 who are extremely clinically vulnerable.

“We would go a step further and urge caution in seeking to apply the findings of this study to those at highest risk from COVID-19 complications…

The experiment demonstrated that adding molnupiravir to standard treatment sped up recovery time and decreased viral detection and load (in a small virology substudy).

The shorter and prolonged symptom reduction, together with the effects on viral clearance, may be key factors in high-risk environments, such as nursing homes, for minimizing the transmission of infection among high-risk individuals.

Molnupiravir might also help healthcare systems, especially when there are a lot of sick people in a community, by letting health workers go back to work sooner and safely, according to the professor who was not involved in the study.

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