Indication of molnupiravir-associated mutations in SARS-CoV-2 sequencing
medrxiv.org
medrxiv.org
"New variants of SARS-CoV-2 are generated through acquisition of mutations that enhance properties including immune evasion and intrinsic transmissibility (Telenti et al., 2022; Carabelli et al., 2023). The impact of molnupiravir treatment on the trajectory of variant generation and transmission is difficult to predict.
On the one hand, molnupiravir increases the amount of sequence diversity in the surviving viral population in the host and this might be expected to provide more material for selection to act on during intra-host evolution towards these properties that increase fitness. However, a high proportion of induced mutations are likely to be deleterious or neutral, and it is necessary to consider the counterfactual to molnupiravir treatment.
As molnupiravir results in a modest reduction in viral load in treated patients (Khoo et al., 2022), it is possible that in the absence of treatment the total viral load would be higher and chronic infections might persist for longer.
Variants generated through chronic infections might be fitter than those that have accumulated mutations during molnupiravir treatment, albeit taking a much longer period of time to accumulate the same number of mutations and therefore usually being derived from older, rather than contemporary lineages.
At the time of writing we have not identified a molnupiravir-implicated cluster that had spread to more than 21 individuals."
Figure 8 is also interesting, as it shows the mutagenic nature of molnupiravir compared to a placebo.
"For the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate."
Basically the drug worked well but the risk of the mutations were high enough that it's only recommended for patients at serious risk of severe Covid who can't take any other therapeutics (primarily Paxlovid). Without vaccines and other treatment options, molnupiravir would have been a very important drug but we developed several alternatives so it'll likely wane to zero new prescriptions over time.
Now, to call it “widely” circulating/spread or “openly circulating in the general public” would be another story
The authors of the study haven't yet identified any molnupiravir-associated lineages that spread to more than 21 people.
If those people were well isolated when they were taking the drug then the mutants wouldn't be transmitted. If the hospitals and homes are well isolated then the mutants won't be transmitted. There is in any case a wide reservoir of virus and mutants in the broader population and it isn't clear that in that broader population that this resistance makes the virus fitter (more likely to be transmitted) and it's likely they are less fit.
The really infective versions seem to have come from immune compromised patients who were infected and likely infectious (not just sick like long covid) for months.
Speaking of theories, I have a theory that most people don't actually believe that evolution is real, because they question basic results like this. The only reason they profess to believe that evolution is real is because that is the only socially acceptable option.