Molnupiravir linked to COVID mutations

The first oral antiviral approved for use in Australia to combat COVID-19, molnupiravir (sold as Lagevrio), is under the microscope.
 
The pill is Australia’s most widely used COVID oral antiviral, having been dispensed more than 640,000 times since it was added to the PBS in March 2022, but according to new research out of the UK, published in Nature, it could also be fuelling COVID-19 mutations.
 
Molnupiravir works by creating mutations in the virus genome during replication, with the aim of weakening or killing it.
 
However, a review of SARS-CoV-2 sequencing databases has also revealed ‘extensive evidence’ of molnupiravir mutagenesis, which can occur when patients treated with the drug do not fully clear the infection and spread the mutated viruses on to other people.
 
To generate their results, scientists searched through global sequencing databases containing more than 15 million SARS-CoV-2 genomes to identify specific mutations in sequences from 2022, after the introduction of molnupiravir.
 
They found many of the countries with these specific mutations, including Australia, the UK, America, and Japan, reported widespread use of molnupiravir.
 
Countries where the drug was not used, such as Canada, had a lower number of mutations.
 
‘These results indicate that molnupiravir treatment has produced a signature mutation profile that is identifiable in sequence databases, a finding that should be considered when assessing the effects and safety of this drug,’ the study said.
 
At this stage, there is no evidence to suggest that the drug has led to the emergence of any new variants of concern, with GP and virology expert Dr Tammra Warby telling newsGP that the research’s significance remains to be seen.
 
As such, she has said GPs should not change their use of molnupiravir for patients who need it.
 
‘A mutated virus that then becomes more fit can be better at transmission or can potentially escape treatments,’ she said.
 
‘As yet we do not know the clinical significance of a particular kind of mutation being potentially associated with medication use.
 
‘If that medication is potentially lifesaving and has an emerging role in prevention of long-term effects of COVID, then its benefit far outweighs the as yet unknown clinical significance of a different viral population.’
 
Last year, molnupiravir generated substantial debate among clinicians, with government health officers urging GPs to not dismiss the medication, despite National COVID-19 Clinical Evidence Taskforce advice that it not be routinely used afters clinical trials suggested that it does not reduce hospitalisation or death rates.
 
Dr Warby said the risks and benefits of COVID treatments, including medications, should be the subject of ongoing research.  
 
‘We are very lucky to have options such as vaccination and medication to treat or mitigate against COVID-19,’ she said. 

‘We did not know the long-term effects of certain viruses, such as of human papillomavirus causing cervical cancer or of end-stage immunosuppression in HIV, for many years.
 
‘It’s imperative that research continues, and in the meantime mitigation of spread and other public health measures such as air ventilation and vaccination are vital.’
 
Merck, the pharmaceutical giant rolling out the drug, has refuted the research.
 
‘The authors assume these mutations were associated with viral spread from molnupiravir-treated patients without documented evidence of that transmission,’ it said in a statement.
 
‘Instead, the authors rely on circumstantial associations between the region from which the sequence was identified and timeframe of sequence collection in countries where molnupiravir is available to draw their conclusions.’
 
The new research comes as the Australian Bureau of Statistics (ABS) revealed COVID-19 was the third leading cause of death in 2022.
 
It is the first time an infectious disease has placed in the top five causes of death since 1970, when influenza and pneumonia were ranked fifth.
 
COVID-19 accounted for more than 5% of all Australian deaths last year, behind only ischaemic heart disease and dementia.
 
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