New strains may be setting up major Covid-19 waves overseas. So what does that mean for New Zealand? Image / CDC
New Zealand's next Covid-19 wave might not be driven by one virus variant, but several at once – and may begin sooner than we think. Jamie Morton explains.
At a passing glance, it appears a single variant, denoted by a single Greek letter, is what's driving a pandemic still infecting hundreds of thousands of people each day.
According to the World Health Organisation (WHO), Omicron accounted for 99.9 per cent of all globally sequenced samples last month – and the picture here in New Zealand is no different.
While it might appear we're sitting in a comfortable, stable pattern under the ultra-dominant Omicron, the sheer amount of change going on within its now-enormous family suggests otherwise.
New derivatives are sprouting up at an astounding pace – more than 200 have been recorded so far – and some are demonstrating a troubling ability to evade the immunity we've built against the virus.
Kiwis might be familiar with the original Omicron type BA.1 and sub-variant BA.2, which both began washing over our population late last summer, or BA.4 and BA.5, which drove a winter surge that pushed daily cases past the 10,000-mark in July.
Around the world, BA.5 currently made up more than 81 per cent of sequenced samples, followed by BA.4 (8.1 per cent) and BA.2 (2.9 per cent).
Within each of these groups are stand-out players that have been catching the attention of scientists.
Updated fit of global SARS-CoV2 lineage frequencies based on all @GISAID + @CovidGenomicsUK data, with special emphasis on latest emerging lineages BQ.1*, BA.2.3.20 & BA.2.75.2, which have large growth advantage & potential to drive a new wave. 🧵 pic.twitter.com/5lMDe0gKFq
— Tom Wenseleers (@TWenseleers) September 25, 2022
Take BA.2.75.2, a third-generation off-shoot of BA.2 that, while making up just 1 per cent of Covid-19 cases, has now been detected in nearly 50 countries.
Nicknamed Centaurus, it's genomically more distinct from Omicron than Delta was from ancestral strains of the coronavirus - yet WHO nevertheless considers it an "Omicron subvariant under monitoring".
It's thought to be nearly seven times tougher for our immune systems to block than BA.5 - and is now considered the most resistant variant seen yet.
Scientists have pin-pointed two specific mutations that make it better able to latch onto our cells and infect us: even if we'd already been exposed to its relatives.
In one recent pre-print study, Chinese researchers estimated it to be, on average, more than six times more likely to reinfect someone who'd had BA.2 - and 2.7 times more likely to cause a reinfection in a person who'd had BA.5.
Another Swedish study has also indicated virus-fighting antibody levels may be five-fold lower against BA.2.75.2 than BA.5.
Other newly emerged BA.2 types packing a concerning array of new mutations include BA.2.10.4, BJ.1, and BS.1.
Meanwhile, BA.5 descendant BQ.1.1 has been popping up around the world and indicating its own potential at evading immune antibodies – but it's so new that little is known about it.
Rather than one distinct variant flattening another – as Omicron did Delta, and Delta did Alpha before that – scientists are now observing sub-forms co-circulating, but changing separately.
This, documented in everything from birds to bacteria, is what's known in biology as convergent evolution: different species of an organism developing similar traits, in response to similar pressures.
Dr Joep de Ligt, ESR'S bioinformatics and genomics lead, said these new sub-forms indeed all appeared to show the same immunity-evading characteristics in their spike protein.
"Yet they don't appear to be trying to out-compete each other."
It's no longer "BA.5 replaces BA.2 replaces BA.1". Next wave involves multiple highly immune-escaping variants circulating at the same time. Several may be rising simultaneously where you are. In the US, Cerberus (BA.2.75), Aeterna (BA.4.6), and Minotaur (BF.7) all increasing. pic.twitter.com/OZxjr5N5tn
— T. Ryan Gregory (@TRyanGregory) September 28, 2022
BA.2.75, for instance, itself produced a mass of new lineages through a major outbreak in the US, and, in its various forms, was persisting globally.
"There's also BA.4.6, which we've seen in a small uptick here."
In the UK, its prevalence jumped from 3.3 to 9 per cent of sequenced samples: a similar proportion to what's being recorded in the US.
The big question facing scientists was whether these convergently evolving, clever new sub-types will power major waves – even in populations now well-exposed to Covid-19.
"We can say with certainty that something is coming," University of Basel viral evolution expert Dr Cornelius Basel told Science.
"Probably multiple things are coming."
Already, there were signs of that happening in a Northern Hemisphere heading into winter, with cases and hospitalisations appearing on the rise in Denmark, Belgium and the UK.
In Germany, where reported cases tripled in three weeks to reach 96,000 on September 29, the country's federal minister of health Karl Lauterbach told media another wave had begun.
Experts here have been watching closely.
"It very much looks like a new wave is starting in Europe, and not with a single variant, but a set of them that all share similar mutations," said Professor Michael Plank, of Covid-19 Modelling Aotearoa.
"I think we'd have to expect a similar pattern happening here."
After weeks of daily cases bouncing around between 1000 and 2000, de Ligt said there had been a slight uptick of about 300 over recent days – but that didn't herald another surge.
"We might simply be seeing factors like reduced masking, or people travelling again coming into play," he said.
"It likely just shows that our last wave isn't quieting down as quickly as it could."
While the removal of border testing had left the picture somewhat less clear, importantly, the latest surveillance data from wastewater sampling hadn't shown any tell-tale shifts in variant activity.
And across hospitals, the most recent sequencing data showed BA.5 making up 87 per cent of samples, followed by BA.4.6 (5 per cent), BA.4 (2 per cent), B.A2.75 (2 per cent) and BA.2 (2 per cent).
"This is probably due to BA.5 having been around here only quite recently, so still reducing the number of susceptible hosts for those other lineages," de Ligt said.
"But going forward, I think we're headed toward a period of stable co-circulation between variants, as Europe and the US appear to be seeing with the beginnings of winter waves.
"Depending on what happens with tourism and travel, these might then work their way here."
This could even happen within weeks, Plank said.
"If the Northern Hemisphere gets a sizeable wave, then I'd expect we'd soon see a wave here, too."
While widespread, recent exposure to BA.5 didn't necessarily make us any less vulnerable to an influx of new lineages, Plank said other behavioural factors could play in our favour.
"Our borders might be open, but in the Northern Hemisphere, it's getting colder and people are starting to go back to school and university, whereas we're heading in the opposite direction."
University of Auckland computational biologist Dr David Welch agreed a re-opened New Zealand would inevitably be affected by big waves elsewhere.
"Just what variants are in the mix, it's hard to say – but with increased travel and lower testing at the border, we can expect them to arrive faster than ever."
Welch said it was possible that several smaller sub-types with different growth advantages could make a similar splash BA.5 did on its own over winter.
"This is why I think it's going to be important to get new bi-valent vaccines and make them accessible to everyone, so we can further increase our population immunity."
The UK has already approved a bivalent vaccine designed to work against the original BA.1 Omicron variant, as well as the ancestral Sars-CoV-2 strain that our current vaccines and boosters target.
BA.1-based bivalent boosters have also just been approved by Health Canada, the European Medicines Agency, and by regulators in Australia, where citizens as young as 30 were also given the option of getting a fourth dose several months ago.
The US has gone further, with the Food and Drug Administration (FDA) approving new BA.5-targeted boosters from Pfizer and Moderna in August.
But vaccine experts here say most Kiwis should be relatively well shielded against the very worst impacts of Covid-19 for now - and don't see great urgency to replace boosters we have already.
As to whether the pandemic's legacy would be an ever-growing assortment of Omicron types, Welch said we still couldn't rule out a completely new variant changing the game.
"This virus has surprised us on several occasions, and I'd expect it's likely to again."
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