Should you’re aged over 70, or over 50 with underlying well being circumstances, and have examined constructive for COVID, you may need been supplied free or subsidised antivirals.
Earlier within the pandemic, these medicines had been an necessary technique to scale back the possibility of individuals changing into severely ailing with COVID, needing to be hospitalised, or dying.
However our new research means that with excessive ranges of vaccination and immunity from earlier infections, COVID antivirals are now not working as properly.
From no therapy to an efficient one
When SARS-CoV-2, the virus that causes COVID, first emerged in late 2019, no therapy was accessible. Present influenza antivirals, which had been stockpiled by governments, had been ineffective and couldn’t be used.
Scientists quickly tried to determine which present or new medication could possibly be used. In 2021, two industry-sponsored scientific trials reported promising outcomes.
One was for nirmatrelvir-ritonavir (Paxlovid), which reported an 89% discount in extreme sickness. The opposite was a trial of molnupiravir (Lagevrio), which reported a 30% discount.
Paxlovid and Lagevrio work by stopping SARS-CoV-2 from replicating. In order that they must be taken early in the midst of sickness – inside 5 days – to be efficient.
Each medication grew to become accessible in Australia and had been listed on the Pharmaceutical Advantages Scheme (PBS) in early and mid-2022. This ensured individuals most vulnerable to extreme sickness had entry to medication at low or no price.
Paxlovid and Lagevrio are costly. A course of therapy price the federal government round A$1,100 from 2022 to 2025, rather more than the therapy for influenza, oseltamivir (Tamiflu), which is barely round $40.
Between mid-2022 and mid-2025 the Australian authorities spent greater than $2 billion on Paxlovid and Lagevrio.
What’s totally different now?
Most Australians have now been vaccinated in opposition to COVID and contaminated with SARS-CoV-2 greater than as soon as. This leads to hybrid immunity and reduces the chance and severity of future infections.
The virus itself has additionally modified, with the unique variants changed by new ones that look like much less extreme than early within the pandemic.
These modifications prompted us to guage the more moderen proof.
What did we research and discover?
First, we examined randomised managed trials – the gold normal of proof. We discovered eight trials of Paxlovid and Lagevrio, however most had been accomplished earlier than individuals had been vaccinated.
After we seemed on the two randomised management trials in vaccinated individuals, neither reported a discount in extreme outcomes after taking both Paxlovid or Lagevrio.
The Lagevrio trial reported no statistical distinction in hospitalisation or demise in individuals who did and didn’t obtain therapy.
The opposite was a trial of people in hospital who had been handled with Paxlovid. It discovered no distinction within the individuals handled and never handled.
There have been some nuances to those findings. Randomised managed trials are costly and resource-intensive. As COVID went from being the main explanation for demise worldwide in 2021 to the twentieth in 2023, it grew to become harder to justify the prices and recruit enough participants, so some trials had been stopped early.
Nonetheless, two randomised controlled trials of Paxlovid have been revealed since our work, and neither reported a discount in hospitalisation or demise.
In section two of our analysis, we seemed on the 35 observational research, the place researchers can embrace many extra individuals however can’t management who will get the therapy. We pooled the outcomes from the research to estimate the effectiveness for every drug in opposition to hospitalisation and demise.
This meta-analysis discovered Paxlovid, however not Lagevrio, lowered hospitalisation and demise.
Paxlovid was related to a 40% discount in hospitalisation and a 67% discount in demise.
Lagevrio wasn’t related to a major discount in hospitalisation and the outcomes had been combined in opposition to demise.
As a result of the therapy wasn’t randomised, there could also be variations between individuals who obtained therapy and people who didn’t. Folks accessing therapy, for instance, could have higher well being literacy or entry to different well being companies.
Whereas some research use strategies to regulate for variations in individuals who do and don’t obtain therapy, it’s normally not attainable to regulate for each distinction.
COVID continues to be a priority for at-risk teams
SARS-CoV-2, like influenza and respiratory syncytial virus (RSV), stays a typical explanation for acute respiratory sickness in Australia. In 2025, there have been:
- 186,000 circumstances of COVID reported
- 178,000 circumstances of RSV
- 503,000 circumstances of influenza.
However the variety of COVID, RSV and influenza circumstances reported is properly under the true quantity, as most individuals don’t get examined.
COVID continues to be claiming lives. There have been 2,227 deaths involving COVID in 2025. That is greater than the 1,784 deaths involving influenza. Three quarters of deaths had been amongst individuals aged 80 and over.
The charges of COVID-related hospitalisations to date this yr have been decrease than final yr, with 839 admissions at “sentinel hospitals” (these chosen to observe illness developments) within the first half of this yr. This compares to 1,740 in the identical interval final year.
What does this imply?
COVID can nonetheless trigger extreme sickness, hospitalisation and demise, significantly in older individuals.
Should you check constructive for COVID, speak to your GP about whether or not antivirals could also be acceptable for you.
Our work reveals there could also be some profit from Paxlovid. However because the variety of circumstances and the chance of extreme sickness continues to fall, this profit is changing into very small.
Given how little proof there may be for Lagevrio, its function in treating COVID must be fastidiously thought-about.
Harms of antivirals can embrace uncomfortable side effects – similar to style modifications, nausea and vomiting – and allergic reactions.
Paxlovid can even interact with other drugs, inflicting critical reactions. It must be averted, or the dose adjusted, in individuals with extreme liver or kidney illness as a result of it may make these circumstances worse.
Australia’s unbiased Pharmaceutical Advantages Advisory Committee (PBAC) is about to evaluate COVID antivirals later in 2026. It’ll assess the prices and advantages of Paxlovid and Lagevrio and it could change its suggestions about who can entry the medication on the PBS.
Our findings assist this reassessment.
