It’s an ongoing question: how effective is molnupiravir when it comes to treating COVID-19? Recent studies have answers that reflect the state of play.
First things first: treating COVID-19 infections with molnupiravir does not decrease deaths or hospital admissions in high-risk, vaccinated patients. It does, however, speed up their recovery process, as a recent Lancet study now suggests.
In this randomized controlled trial with 25,708 participants from health centers across the UK, patients recovered more quickly when taking molnupiravir compared to those in the trial’s control arm. A higher risk of hospitalization or death was defined for patients who were 50 years or older, or 18 years or older with relevant medical conditions. The participants had a confirmed omicron infection and experienced symptoms for five days or less before beginning treatment. About half of the participating patients (12,774) received a dosage of molnupiravir (800 mg twice daily for five days), taken at home, in addition to standard care. The control half (12,934) solely received standard care.
The trial’s main concern was to find out whether molnupiravir reduces the risk of hospitalization or death. Secondary objectives were related to recovery time and symptoms. All participants reported via an online diary during a 28-day follow-up. As stated before, no benefit was observed in hospitalization or death rates between the molnupiravir and control group. There were 105 cases of death or hospitalization (0.8 %) in the treatment group, versus 98 cases of death or hospitalization in the control group (0.8 %). Participants treated with molnupiravir also reported more favorable outcomes for many secondary outcomes. The median average length of illness in these patients was 9 days (15 days in the control group). Accounting for the range of recovery times across both groups, this translates to a faster recovery in the molnupiravir group (4.2 days quicker on average). 7 patients in the control group did not reach recovery within the 28-day follow-up. A relatively lower number of molnupiravir patients sought further medical care after completing the trial (20 % of molnupiravir patients, 24 % of the control group).
An important and new aspect: participants were vaccinated and suffered from omicron infections. Previous studies suggested that the antiviral agent could help prevent hospital admissions in patients with mild to moderate infections, but these trials were conducted among unvaccinated participants and before the emergence of omicron. The importance of this factor regarding the formulation of further strategies for this COVID-19 winter should not be underestimated, as the authors of this latest study stress. The study reflects the present situation in the UK more accurately, as the authors state. Since molnupiravir is among the more expensive alternatives when it comes to treating COVID-19 (a seven-day treatment costs around 0 in the US, compared to about 0 for a five-day treatment of Paxlovid®), they also caution that the assumed benefits of molnupiravir need to be considered with regards to cost-effectiveness and an already strained healthcare system.
However, this study was not the only blow for molnupiravir in recent days. An Australian research group published an admittedly small case-control study in which the SARS-CoV-2 virus genome evolution was monitored in nine immunocompromised patients. Five of the patients were treated with molnupiravir, the other four did not receive any antivirals during the study period. The question was, whether molnupiravir treatment facilitates the emergence of mutated versions of SARS-CoV-2. Accrual of mutations in immunocompromised patients and subsequent release into the wild is being discussed as a possible mechanism behind the emergence of new virus variants.
Molnupiravir reduces viral replication in COVID-19 patients by inducing mutations throughout the genome. This does not necessarily mean that it facilitates virus evolution. But the Australian study, so far only published as a preprint, points into this direction. Within a few days, the researchers detected a large number of mutations in patients on molnupirvair treatment. Some of these mutations managed to establish themselves in the virus population of the carrier. Such successful intra-individual evolution is considered a pre-requisite for onward transmission into the community, although, in this study, it was not analysed whether the individuals were actually infectious and thus capable of virus transmission.
The researchers did not observe similar mutation development in control patients without molnupiravir treatment. Given these results, the Australian researchers think that molnupiravir treatment in immunocompromised COVID-19 patients might supercharge SARS-CoV-2 evolution and thus ultimately lead to new variant-driven waves of the pandemic. It is not clear at the moment whether nirmatrelvir/ritonavir, better known as Paxlovid®, has similar effects when administered to immunocompromised patients. But many experts consider this to be likely, since antiviral treatment that does not result in virus elimination – as in immunocompromised patients – is always a selection force which has also been shown for treatment of immunocompromised patients with convalescent plasma earlier in the pandemic.
This article was written by Lena Meyer-Woters and Philipp Grätzel.
Image source: Susan Q Yin, unsplash