Covid pill being rolled out among vulnerable Britons could fuel dangerous mutations, experts warn


The rollout of a new Covid pill among thousands of vulnerable Britons this winter needs to be closely monitored amid concerns it could help to fuel the emergence of dangerous mutations, scientists have said.

Molnupiravir is to be made available to roughly 5,000 people infected with Covid as part of a national study called Panoramic. Participants will be aged 50-plus or classified as clinically vulnerable, and will have been infected for less than five days.

The antiviral pill, which cuts the risk of hospitalisation or death from Covid by 30 per cent, has been approved for use by Britain’s medicines regulator, but scientists are concerned it could unintentionally drive the creation of new variants in patients with weakened immune systems.

Professor Lawrence Young, a virologist at the University of Warwick, said the “mutagenic effect” of molnupiravir “on the virus itself remains a concern”.

Immunocompromised people taking the pill should be given other therapies at the same time “to avoid the generation of resistance”, warned Emma Thomson, a clinical professor of infectious diseases at the University of Glasgow.

Molnupiravir works by interfering with the replication of the Covid virus once it’s gained entry to our cells. The drug introduces mutations to the Sars-CoV-2 genome, leading to a build-up of copy errors that weaken the virus and prevent it from further replicating, allowing the body to clear it.

But some experts have warned that, during this period of mutation accumulation, a “fitter” version of the virus may arise which is able to continue replicating in the body before being transmitted on to others. It’s thought this risk is only likely in immunosuppressed recipients of the pill, given their difficulty in fighting infections.

“The patient group that one would be most concerned about are immunosuppressed individuals, as viral clearance needs not only restrained viral replication but also an intact functioning immune system to clear the virus-infected cells,” said Penny Ward, a visiting professor in pharmaceutical medicine at King’s College London.

“We have seen before that transmissible viruses resistant to antiviral treatments arise more frequently in this population than in people with intact immune systems.”

Dr Stephen Griffin, a virologist at the University of Leeds, said it “may be wise to avoid treatment of long-term persistent [Covid] infections within immunocompromised individuals as changes may be more likely to become established.”

The Panoramic study has begun recruiting for 5,300 people who have been unwell with Covid for less than five days.

Those at the highest risk from Covid – such as the immunocompromised and people suffering from cancer and heart disease – can receive the treatment from 16 December as part of the study, the government has said.

The emergence of new variants driven by molnupiravir has yet to be observed in laboratory, animal or human testing, but Prof Young said a higher prevalence of mutations were found among Covid patients in the treatment arm of the drug’s phase two trial, compared to the placebo.

Analysis showed that these mutations were located in the spike protein of the virus, which is the target of Covid vaccines, and “were similar to those seen in major variants, including delta,” said Prof Young.

The clinical trials for molnupiravir, developed by Merck, included patients who were immunocompromised, but “the actual number enrolled was very small – too small to make any definitive conclusion,” said Prof Ward.

Merck has implemented a viral surveillance programme to try to detect the emergence of variants as molnupiravir is used more widely in humans. In the UK, the Panoramic study will also investigate this risk.

Molnupiravir is taken twice a day for five consecutive days. At the appropriate dosage, it’s “highly likely” that the drug will be effective, said Dr Griffin. However, he added, “sub-optimal dosing could be an issue.”

It is important that people take all their prescribed pills, otherwise it “may lead to the same problems we have when folk don’t complete their course of antibiotics,” said Prof Young.

He and Prof Ward both suggested that molnupiravir should be combined with Pfizer’s antiviral drug, known as Paxlovid, to treat immunosuppressed people recently infected with Covid “as this may reduce the emergence of [a] resistant virus”.

Early data suggest that Paxlovid is nearly 90 per cent effective in cutting the risk of hospitalisation and death among vulnerable individuals. It works differently from molnupiravir, too, and does not drive mutations in the same way.

The government has secured enough supplies of molnupiravir and Paxlovid to treat more than 700,000 people in the UK.

Aris Katzourakis, a professor of evolution and genomics, said he did not share the concern of others and questioned whether molnupiravir would lead to the emergence of new variants.

However, he advised “monitoring chronically infected individuals, such as certain immunocompromised patients, to determine any impacts in terms of viral sequence change.”

Prof Thomson said that molnupiravir “might well drive mutations” but was unsure it would accelerate evolution in favour of new variants. Prof Ward said the phenomenon, for now, remains a“theoretical concern”.

A Merck spokesperson said the claim that molnupiravir could drive dangerous mutations in patients was “unfounded” and has “no scientific basis or merit.” They added: “There is no evidence to indicate that any antiviral agent has contributed to the emergence of circulating variants.”

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