Molnupiravir speeds up recovery and eases long-term symptoms, but its minimal effect on hospitalizations raises questions about its broader impact on COVID-19 care.

Study: Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial. Image Credit: Audio und werbung / Shutterstock

In a recent study published in The Lancet Infectious Diseases, researchers evaluated the effects of the antiviral drug molnupiravir treatment for coronavirus disease 2019 (COVID-19) on various health outcomes.

Although COVID-19-related hospitalization and mortality are currently rare, acute infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain common, with longer-term symptoms continuing to present a significant public health burden.

A survey in the United States has estimated that one-tenth of adults infected with SARS-CoV-2 experience long COVID or post-COVID-19 condition. Long COVID is defined as symptoms originating or aggravated by COVID-19 that persist beyond 12 weeks without an alternative disease.

Trials have shown that treating acute infection with novel antivirals can decrease hospitalization, recovery duration, and viral detection and load more than placebo in non-vaccinated individuals. A community trial (PANORAMIC) previously noted no additional reduction in the already lower risk of hospitalization with molnupiravir in vaccinated individuals with COVID-19.

Nevertheless, molnupiravir expedited recovery and helped them stay well more often. Further, retrospective observational analyses have observed potentially modest effects of COVID-19 treatment with molnupiravir on post-COVID-19 condition and related symptoms. However, these studies relied on diagnostic codes and did not directly evaluate the effect on well-being, health-related quality of life, and education or work.

About the study

In the present study, researchers evaluated the effects of COVID-19 treatment with molnupiravir on symptoms, well-being, medication use, new infections, and social and healthcare use. Eligible participants were aged ≥ 18 with a comorbid condition or ≥ 50, had ongoing symptoms from COVID-19 that started within the past five days and tested positive for SARS-CoV-2 within the past week.

Between December 8, 2021, and April 27, 2022, participants were randomized to molnupiravir plus usual care or usual care alone. Randomization was stratified by vaccination status and age. The study’s primary outcome was hospitalization, death, or both at 28 days. Secondary outcomes included any longer-term outcomes. Online questionnaires were administered three and six months after randomization.

Participants were asked to rate symptoms on a four-point scale and how well they were feeling on a 10-point scale. They were asked to specify if they were hospitalized, had any contact with social and health care services, and whether they took time off study or work. Other outcomes were household COVID-19 cases, use of prescribed or over-the-counter medications, and health-related quality of life.

Findings

The study randomized 12,821 participants to usual care plus molnupiravir and 12,962 to usual care alone. Over 89% of participants provided information for at least one follow-up time point; these subjects were comparable to the whole sample. The use of other medications was rare; only 0.2% reported using monoclonal antibodies, and 1.3% reported corticosteroid use for COVID-19.

Serious adverse events occurred in 0.4% of the molnupiravir group and 0.3% of the usual care group within the first 28 days. Seventeen deaths occurred in the molnupiravir group and 10 in the usual care group. There was a small but notable difference in wellness ratings between groups at three and six months, favoring the molnupiravir group. Fewer individuals in the molnupiravir group reported any moderately bad or worse symptoms at three and six months.

Moreover, fewer molnupiravir participants reported any persistent symptoms at both time points. Social or healthcare service use was lower in the molnupiravir group. Fewer subjects in the molnupiravir group reported taking time off study or work at either time point. COVID-19-related or all-cause hospitalization rates were similar between the groups.

Besides, the molnupiravir group had fewer COVID-19 cases in the household at three months. However, this trend was reversed by the six-month mark, with more new household cases in the molnupiravir group. Use of medication was lower in the molnupiravir group at three months but not at six months. Health-related quality of life was better in the molnupiravir group at both time points. The results of the sensitivity analyses were not different from those of the primary analysis.

Conclusions

Taken together, the study investigated the longer-term effect of molnupiravir for COVID-19 treatment. The researchers observed that cough, dyspnea, unwellness, fatigue, and muscle aches were less prevalent in the molnupiravir group. However, the differences were modest, and the absolute effect sizes were small. Time off work, persistent symptoms, wellness ratings, worse or moderately bad symptoms, and social or healthcare use were statistically better in the molnupiravir group.