In case you’re aged over 70, or over 50 with underlying well being situations, and have examined optimistic for COVID, you might need been provided free or subsidised antivirals.
Earlier within the pandemic, these medicines have been an essential technique to scale back the possibility of individuals changing into severely sick with COVID, needing to be hospitalised, or dying.
However our new analysis means that with excessive ranges of vaccination and immunity from earlier infections, COVID antivirals are now not working as effectively.
From no remedy to an efficient one
When SARS-CoV-2, the virus that causes COVID, first emerged in late 2019, no remedy was obtainable. Current influenza antivirals, which had been stockpiled by governments, have 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. So that they should be taken early in the midst of sickness – inside 5 days – to be efficient.
Each medication grew to become obtainable in Australia and have been listed on the Pharmaceutical Advantages Scheme (PBS) in early and mid-2022. This ensured folks most liable to extreme sickness had entry to medication at low or no value.
Paxlovid and Lagevrio are costly. A course of remedy value the federal government round A$1,100 from 2022 to 2025, rather more than the remedy for influenza, oseltamivir (Tamiflu), which is just 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 judge the newer proof.
What did we examine and discover?
First, we examined randomised managed trials – the gold customary of proof. We discovered eight trials of Paxlovid and Lagevrio, however most have been completed earlier than folks have been vaccinated.
After we appeared on the two randomised management trials in vaccinated folks, 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 remedy.
The opposite was a trial of individuals in hospital who have been handled with Paxlovid. It discovered no distinction within the folks 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 reason behind demise worldwide in 2021 to the twentieth in 2023, it grew to become tougher to justify the prices and recruit sufficient contributors, so some trials have been stopped early.
Nonetheless, two randomised managed trials of Paxlovid have been revealed since our work, and neither reported a discount in hospitalisation or demise.
In part two of our analysis, we appeared on the 35 observational research, the place researchers can embody many extra folks however can’t management who will get the remedy. 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 have been combined in opposition to demise.
As a result of the remedy wasn’t randomised, there could also be variations between individuals who obtained remedy and people who didn’t. Folks accessing remedy, for instance, might have better 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 remedy, it’s normally not doable 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 reason behind 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 effectively 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 have been amongst folks aged 80 and over.
The charges of COVID-related hospitalisations to this point 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 yr.
What does this imply?
COVID can nonetheless trigger extreme sickness, hospitalisation and demise, significantly in older folks.
In case you check optimistic for COVID, discuss to your GP about whether or not antivirals could also be applicable 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’s for Lagevrio, its position in treating COVID needs to be fastidiously thought-about.
Harms of antivirals can embody uncomfortable side effects — akin to style modifications, nausea and vomiting — and allergic reactions.
Paxlovid may also work together with different medication, inflicting severe reactions. It needs to be averted, or the dose adjusted, in folks with extreme liver or kidney illness as a result of it will possibly make these situations worse.
Australia’s unbiased Pharmaceutical Advantages Advisory Committee (PBAC) is ready to evaluate COVID antivirals later in 2026. It would assess the prices and advantages of Paxlovid and Lagevrio and it might change its suggestions about who can entry the medication on the PBS.
Our findings assist this reassessment.
Revealed on August 24, 2026
