Molnupiravir cuts risk for severe COVID-19 symptoms — and possibly long COVID
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Key takeaways:
- The antiviral reduced the risk for severe symptoms of COVID-19, need for health care and time off of work after recovery.
- The trial may inform future studies on treatment and prevention of long COVID.
The antiviral molnupiravir modestly reduces the risk for severe symptoms of COVID-19 and may also reduce the risk for long COVID, according to a randomized controlled trial.
In 2021, the MOVe-OUT trial demonstrated that molnupiravir — one of three antivirals available to treat COVID-19 in the United States — reduced the risk for hospitalization or death from COVID-19 by around half among unvaccinated participants.
In contrast, the PANORAMIC trial showed that molnupiravir did not reduce the risk for hospitalization from COVID-19 among vaccinated adults, but did speed recovery by 4 days, the authors of the new analysis noted.
In a follow-up to PANORAMIC, researchers randomly assigned more than 25,000 adults to receive either molnupiravir plus usual care (12,821) or only usual care (12,962) between Dec. 8, 2021, and April 27, 2022. Participants were aged at least 50 years or at least 18 years with a comorbidity, and 99.1% had received a previous dose of COVID-19 vaccine.
The researchers found that vaccinated participants treated with the antiviral experienced fewer and less severe COVID-19 symptoms, accessed health care less often and took less time off work 6 months after recovery, “but with small effect sizes” and “high numbers needed to treat.”
Specifically, among participants in the treatment arm, molnupiravir was associated with a 1.9% reduction in severity of any severe symptoms and a 2.5% reduction in severity of persistent symptoms after 6 months. The number of participants needed to treat to achieve the benefit were 52.6 and 40, respectively.
“The promising results from the PANORAMIC trial are consistent with results from well-conducted observational analyses as they both converge on finding a modest effect of molnupiravir in reducing the risk of long COVID in high-risk individuals,” Ziyad Al-Aly, MD, chief of research and development services at Veterans Affairs St. Louis Health Care System, wrote in a commentary published with the study.
We asked Al-Aly, who was not involved in the trial, about the significance of the findings for COVID-19 treatment and the prevention of long COVID. His answers have been lightly edited for clarity.
Healio: What stuck out to you in the results of the study?
Al-Aly: I have been waiting for the results of this large, randomized study. It clearly shows that molnupiravir reduced the risk of several important outcomes. The effect size is small, but not negligible.
Healio: What’s the bottom line on antivirals and long COVID?
Al-Aly: As it stands, the current evidence suggests that antivirals have an effect in reducing the risk of long COVID. This is evident in PANORAMIC (molnupiravir) and a study on ensitrelvir, another antiviral from Japan. It is also clear from these studies that the effect size is small — meaning that we cannot solely rely on antivirals to completely prevent long COVID.
Healio: What should clinicians take from these findings?
Al-Aly: In high-risk individuals, antivirals reduce the risk of severe COVID-19 illness and may also reduce the risk of long COVID. They remain massively underutilized. Clinicians should be cognizant of adverse events, drug-drug interactions (for example, with Paxlovid), and the mutagenic potential of molnupiravir (it induces mutations in SARS-CoV-2). But they should also consider potential benefits.
Healio: What do you hope they take away from your related commentary?
Al-Aly: The PANORAMIC results suggest that blocking viral replication in the acute phase — via molnupiravir — reduced the risk of long Covid. This is an important clue — that hitting the virus early, diminishing its ability to replicate and suppressing viral load may hold promise in preventing long COVID. We need to continue to investigate the role of antivirals in preventing and treating long COVID and figure out ways to optimize their effectiveness. Trials to test combinations of antivirals, longer duration of treatment, etc., should be pursued.
References:
- Al-Aly Z. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(24)00436-5.
- Bernal AJ, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2116044.
- Butler CC, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)02597-1.
- CDC. Types of COVID-19 treatment. https://www.cdc.gov/covid/treatment/index.html. Updated July 12, 2024. Accessed Sept. 18, 2024.
- Harris V, et al. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(24)00432-6.
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