When the Alpha coronavirus variant surfaced in late 2020, it triggered the chaotic closing of British borders and global panic.
The march of Delta the following year sparked similar alarm, and left some experts speculating whether this quicker, deadlier edition of Covid-19 would be pandemic's enduring legacy.
Then, out ofnowhere, came variant B.1.1.529.
Carrying double Delta's count of mutations, and unprecedented power to infect people and escape immunity, Omicron washed over the world at astonishing pace.
Delta's reign was brought to a swift end: as this month, globally reported incidence of it was zero.
While scientists have watched variants come and go, a series of similar successions have been packed into the seven months Omicron has been on the stage: from its original subvariant BA.1, to the faster BA.2, and now, seemingly, to BA.4 and BA.5.
This raised the big question: was Omicron, in whatever form it took, here to stay?
Or, like Omicron, would this Sars-CoV-2 virus surprise us with something completely different?
"In reality, we don't know – but either can happen," Otago University evolutionary virologist Dr Jemma Geoghegan said.
"Compared with other variants of the ancestral strain, Omicron has got really fit – and subtypes out there like BA.4 and BA.5 are all doing well right now."
The reign of Omicron
Omicron's impact in New Zealand can be measured in many ways: be it the near-1300 people who've died with the virus this year, or the fact it's likely infected half the population: eclipsing the 14,206 Covid-19 cases recorded in the pandemic's first two years.
And last month, officials confirmed the arrival of the more infectious BA.2.12.1 subvariant.
With BA.4 and BA.5 now also in the country, experts are watching closely to see whether the latest types might drive a winter wave of reinfections much sooner than first thought.
Earlier this month, a modelling paper focused mainly on BA.2 found a second wave could hit in the second half of the year, driven in part by people getting reinfected because their immunity has waned.
"The fact that BA.4 and BA.5 are here now means we're likely to get that second wave earlier rather than later," Covid-19 Modelling Aotearoa's Professor Michael Plank said today.
The nascent subtypes' edge appeared to be in causing breakthrough infections: one new study indicated that, among vaccinated and boosted people, they could be four times' more resistant to neutralisation than BA.2.
However, BA.2.12.1 was only modestly more resistant to neutralisation than BA.2.
The same study suggested that, among the therapeutic antibodies authorised for clinical use, only bebtelovimab retained full potency against both BA.2.12.1 and BA.4 and BA.5.
Overseas, the European Centre for Disease Prevention and Control just warned that an observed growth advantage within the two subvariants would probably cause a rise in cases over coming weeks – meaning more hospitalisations, ICU admissions and death.
The Ministry of Health's chief science advisor Dr Ian Town last week said the international situation remained further Omicron waves – and New Zealand had been seeing "exactly the same thing with additional sub-variants being detected here over recent weeks".
Where could Omicron go from here?
"That's really hard to say, because we're looking at a race between virus and host," Geoghegan said.
"I'm not sure that there is even a limit for the fitness of this virus to be maximised, because the landscape is changing all of the time – so there's definitely lots of room for it to keep evolving."
Just what created Omicron remains unclear – one theory has it being incubated within a person with chronic infection – but it appeared to have evolved from a strain circulating way back in mid-2020.
University of Auckland computational biologist Dr David Welch said he wouldn't be surprised if the pandemic's next twist was an "Alpha-like event" where a relative of Omicron took centre-stage.
"But are we going to get an event like what we saw with Omicron arising and overtaking Delta? That's harder to see."
Scenarios and surprises
Around the world, scientists have been trying to find possible telltale signs that could forewarn the next seismic shift.
Last month, MIT and Harvard University researchers outlined a machine-learning model capable of analysing millions of coronavirus genomes, and picking which viral variants would likely dominate and cause surges in cases.
Their model, dubbed called PyR0, might also help pinpoint which parts of the virus' genome will be less likely to mutate - and hence make good targets for vaccines targeted against future variants.
More generally, scientists believe that whatever succeeds Omicron will need to be somehow even more contagious – and even better at evading vaccine immunity.
It's possible that might even arise with the virus responding directly to coming Omicron-centred shots - or from somewhere perhaps less expected.
One troubling prospect is a zoonotic spill-back event, in which the virus passes from human to animal - and then back to humans in a smarter form.
"The best example we have to compare this with is influenza, which we see circulate year after year," Geoghegan said.
"It's when we get changes in antigenic novelty that we get those really big flu years.
But every so often, we see a new spillover event – such as what happened with swine flu, which we know was extremely set to spread between humans."
It "probably wouldn't be far-fetched", she said, to see this occur in Omicron.
"The vast number of mammalian hosts that can be infected makes me think that it's actually quite likely."
Already, the coronavirus has been found in whitetail deer, along with a colourful variety of species spanning from cats, dogs and pigs to ferrets, rabbits, fruit bats and hamsters.
Zoonotic spillback happened to be one long-term scenario explored in a recent report out of the UK Government's Scientific Advisory Group for Emergencies (SAGE).
Another included a variant that emerged to cause severe disease in a greater proportion of the population than had occurred to date - such as happened with previous coronaviruses Sars-CoV and Mers-CoV, which had case fatality rates of around 10 and 35 per cent respectively.
Most concerningly, SAGE described Omicron's comparatively milder symptoms as a "chance event".
"The next variant to achieve UK/global dominance is likely to have the same pathogenicity as previous variants."
What NZ can do
If a new and more aggressive variant did arise, Town told media today that surveillance would be important, adding that public health measures were "all there in reserve".
Otago University epidemiologist Professor Michael Baker stood ready to be surprised.
"I think that, yes, we can expect to see a radically different variant that would warrant a new name," he said.
"If you look at the prognostic factors for this virus having the opportunity to make a big evolutionary leap, I think all of the ingredients are there."
Baker pointed out the virus had already demonstrated its ability to dramatically modify its genome, or recombine to take on new forms.
"The second factor is the opportunities it has to evolve are now so vast: even besides the number of infected people across the globe, this is also an epidemic among animal species," he said.
"The big thing we can change is dampening down the burden of infection."
But given Omicron was everywhere, and so successful, that was a tough ask for the world.
"New Zealand can certainly do its part by taking a mitigation approach that's tighter than what we've got now," he said.
"Even though we probably won't be the breeding ground for the next big jump in virus evolution we need to do our bit to dampen down transmission - just as we need to reduce our emission of greenhouse gases to contribute to the global effort to combat climate change."