“COVID-19 is now an established and ongoing health issue which no longer constitutes a public health emergency of international concern.” – Statement on the 15th meeting of the International Health Regulations Emergency Committee on the Covid-19 pandemic.

On May 5 this year, World Health Organization director-general Dr Tedros Adhanom Ghebreyesus declared the pandemic emergency downgraded from an acute global disaster into a more chronic, long-term affliction. Covid-19 became another in the long line of deadly pathogens that have seared their way into history, then faded into the background thrum of human disease.

Except SARS-CoV-2 isn’t just the common cold or another influenza. It is a fiendishly slippery virus that still astounds experts with its ability to morph its genetic code time and time again to get around increasingly widespread and strong human immunity, derived both from vaccines and infection.

“We knew early on this was going to be very significant,” says Associate Professor Paul Griffin, of Mater Health Services and the University of Queensland Medical School in Brisbane, “but I don’t think anyone really predicted the magnitude or the duration of this event.”

Covid vaccines, the first of which was approved in Australia in January 2021, sparked hope when they arrived. Yet while the vaccines marked a turning point, they have not delivered the decisive blow to banish SARS-CoV-2 to medical history. After years of vaccination messaging from federal and state governments, things have gone strangely quiet, leaving everyone from experts to the general public wondering what to do.

The current recommendation from the federal Department of Health and Aged Care is that all adults are eligible for a vaccine booster if it has been six months or more since their last booster or since they had Covid-19. Boosters are especially recommended in adults aged over 65, or those over 18 with chronic health conditions or disability.

For 5 to 17-year-olds, boosters are only recommended for those with health conditions that put them at risk of severe illness, and for whom it’s been more than six months since their last vaccine dose or Covid infection. In Australia, Covid vaccines aren’t recommended for healthy children under five.

Yet that message isn’t cutting through, Griffin says. “We’re getting questions every day about whether six months means ‘every six months’ or whether they’re supposed to be a one-off this year, and what’s happening with the strategy,” he says. “There’s just not a lot out there.”

The waters are further muddied by a drumbeat of reports of new subvariants, each more efficient than its predecessors at getting around pre-existing immunity, both vaccine-derived and infection-acquired.

Gone are the simpler days of Greek alphabet-named variants: the latest World Health Organization weekly epidemiological report talks about variants of interest – XBB.1.5, XBB.1.16 and EG.5 – and variants under monitoring, including BA.2.86, XBB.1.9.1, and others. Some are increasing in prevalence, some are decreasing, some are holding steady.

The good news is that despite the Houdini-like abilities of these variants to evade capture by SARS-CoV-2 antibodies, Covid vaccines are still reasonably good at doing what they were intended to do: keeping people out of hospital.

In 2022, Associate Professor Bette Liu, of the UNSW Vaccine and Infection Research Lab in Sydney, and colleagues, used national Australian datasets to examine the effectiveness of Covid vaccines and boosters at reducing the risk of death in 3.8 million Australians aged 65 and older.

That study, which has not yet been published in a peer-reviewed journal, found that at the beginning of the Omicron wave, in the first few months of 2022, three and four doses of vaccine were highly effective at preventing death from Covid.

“The vaccines provided really good protection,” Liu says. “The estimates at the beginning of 2022 was over 90 per cent effective in preventing death from Covid – so that’s really the pointy end in terms of severity of disease.”

In the latter half of that year, however, Omicron began generating subvariants at a fierce rate. At the same time, the vaccines’ effectiveness against death dropped to 75 per cent for three doses and 84 per cent for four doses.

One complication when trying to measure the ongoing effectiveness of Covid vaccines is that they are being compared to an unvaccinated population. By the second half of 2022, after Australia’s Omicron surge, that population had almost certainly gained a degree of immunity from exposure to Covid, which meant their risk of death was reduced despite being unvaccinated.

It also highlights the challenge of vaccinating against a constantly evolving virus. Since Liu’s study finished, bivalent Omicron boosters became available in Australia, which were designed to offer better protections against the newer subvariants BA4 and BA5. A booster targeting the XBB.1.5 subvariant is also going through an approvals process in the US which, if successful, will likely see it soon approved in Australia.

“There have been a number of studies around the world subsequently showing that the bivalent vaccines do confer a benefit, even compared with the monovalent vaccines, in protecting people both against infection but then also some serious disease outcomes,” Liu says.

Now BA4 and BA5 are being edged out, XBB.1.16 and EG.5 are the most prevalent subvariants globally, and groups such as the WHO and The US’s Centers for Disease Control and Prevention are eyeing the emerging BA.2.86 because of the huge number of mutations in its spike protein, signifying a possible increase in its ability to get around pre-existing immunity.

This “variant soup” is a headache for vaccine manufacturers and governments, who are trying to predict the future in their attempts to get ahead of whatever subvariant is just around the corner.

“We just need to do what we do with flu, which is pick what might be the problem next season and we have to do that in advance,” says epidemiologist Professor Catherine Bennett, of Deakin University in Melbourne. Yet with so many subvariants circulating in different parts of the world, that’s far from straightforward. “It’s that mixed story of probably not having a vaccine specific to every variant,” Bennett says, “but figuring out which is the best given the mix of variants that seem to be dominating, and/or taking into account severity.”

At this point, that could be the XBB.1.5 booster, but if BA.2.86 takes over, then the earlier boosters might be more effective. Bennett says some subvariants seem to be hanging around longer than others, which could suggest they’re the ones more likely to become endemic and therefore a better target for vaccine boosters.

“We need to have an agile vaccine policy-making and procurement process, as the mutations are outstripping the speed of our matched vaccines,” says epidemiologist and infectious diseases expert Raina MacIntyre, professor of global biosecurity at UNSW Sydney. “The vaccines not only wane after a few months, but they are not able to match the newer variants that come along every few months.”

That concern was highlighted in a report on Covid vaccine purchasing and procurement, commissioned by federal Health Minister Mark Butler. The report’s author, Professor Jane Halton, highlighted the need to be able to “rapidly deliver effective vaccines and therapies to large numbers of people”, and have in place supply agreements that allowed for scale-ups in response to spikes in demand. “In the event a new and significantly different variant with severe health outcomes emerges, the capacity to respond rapidly and at scale should remain a policy and delivery priority,” Halton wrote.

There’s also the question of who should get vaccinated and when. Liu’s study showed that the level of protection dropped to about 50 per cent at six months after a booster shot, which lends weight to the current Australian government advice that boosters should be given at six months after the last dose or after infection.

However, the WHO has taken a more relaxed approach. In the latest update of the WHO roadmap on the use of Covid vaccines, the organisation recommends adults aged about 75-80 years and older get boosted every six to 12 months, but those aged 50-60 and without significant health conditions only need a booster every 12 months. For younger adults, adolescents and children without any health conditions, WHO says routine booster vaccinations aren’t recommended at all, saying the benefits are marginal.

Epidemiologist and paediatric infectious diseases expert Professor Peter McIntyre, of the University of Otago in New Zealand, says for adults under the age of 50, and certainly under 30, the combination of vaccine-derived and infection-acquired immunity is likely to be enough protection without the need for regular boosters. “For most of the population it’s going to be repeated infection that’s going to add to the strength of their immunity across the board,” McIntyre says.

However, the spectre of long Covid makes the prospect of repeat infections unappealing to many. “There is now a vast amount of research saying long Covid is also an important outcome, occurring in a significant proportion of the population, even in adults and children,” Raina Macintyre says, pointing out that vaccines do protect against long Covid.

She also argues Australia needs to enable vaccination of healthy children under five – a policy implemented in the United States, but not in the UK, except in high-risk children. “We vaccinate kids under five for all kinds of other infections for which the death rate is not as high as Covid in kids,” she says.

These questions will likely become more pressing in northern hemisphere countries, as they head into their winter, before they need to be addressed in Australia. But despite the current lull in infections, and relatively low disease severity being seen with each new subvariant, Griffin says now is the time to develop a vaccine strategy and communicate it to the general public so the nation is prepared for whatever comes next.

“Another wave is inevitable,” he says. No one can predict which variant or subvariant, whether it will be more or less severe than previous ones, but nothing can be taken for granted. “The only thing we can’t say is which variant or subvariant it will be and when it will be and what magnitude but it’s very likely we’ll be required to recommend a booster in a more widespread fashion when that occurs.”

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