Covid 19 coronavirus: What will the next big variant look like?

New Zealand could likely see variants more potent than Delta turn up at our borders as the Covid-19 pandemic grinds on – but a leading epidemiologist says our elimination strategy can still hold.

This week, the Ministry of Health confirmed that a variant that recently emerged in South Africa, labelled C.1.2, was detected in a local border case in late June.

While the World Health Organisation this week said it didn’t appear to be spreading yet, scientists have been watching it closely given it carried mutations similar to those seen in other variants like Delta.

Otago University epidemiologist Professor Michael Baker said pop-ups like C.1.2 highlighted how easily the virus had been able to spread, change and create new forms of itself.

“We’ve created the perfect environment for it to mutate, and create a whole range of new variants.”

Variants today

From the moment the parent strain or “wild type” of the Sars-CoV-2 virus began its global spread, new variants became an inevitability.

As the virus travelled and replicated, through copying its genome, it sometimes made mistakes – or created mutations.

And if a certain mutation provided some advantage, like more easily invading cells, then it became more likely that it increased in frequency.

Although the coronavirus was evolving at only about half the pace of influenza, its travels around the world had enabled it to evolve and learn how to better infect hosts.

Nearly two years on from the dawn of the pandemic, scientists have identified a large number of variants, four of which are deemed variants of concern because they’re faster-spreading, more virulent, or pose a bigger challenge against vaccines and health measures.

Those four are B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 – better known as Delta.

While Alpha was between 43 and 90 per cent more transmissible than earlier variants, Delta could even be between 30 and 100 per cent more transmissible than Alpha.

It’s estimated that, on average, one person infected with Delta may infect five or six other people – and the variant also posed a higher risk of hospitalisation.

“It does seem to be about as twice as lethal – and it’s putting a higher proportion of people in hospital.”

Mutations within these variants had mostly tended to occur around the virus’ “spike protein”, which it used to bind to the ACE2 receptor that gave it entry to human cells.

One study into Delta suggested a separate mutation could help its ability to fuse with human cells once it latched on – which then allowed it to infect more cells and ultimately overwhelm immune defences.

Meanwhile, scientists have been monitoring another variant, labelled C.37 or lambda – and so far deemed a “variant of interest”, one tier down – that’s been tearing through South America.

But because Delta spread about twice as quickly as the parent strain – and thus could infect more people before its ancestor had a chance to reach them – the variant had become the world’s dominant strain.

While three subtypes AY.1, AY.2 and AY.3, dubbed “Delta Plus”, have grabbed international headlines, there’s still no strong evidence these are any more of a threat than the original variant.

The variants to come

Baker pointed to a recent report by the UK Government’s Scientific Advisory Group for Emergencies (SAGE), which set out four scenarios of the virus’ long-term evolution.

Scientists have suggested that the virus may now have passed through enough people to select its best variant – but it’s still entirely possible that future combinations of mutations could make it even more deadly and transmissible.

One was a variant that emerged to cause severe disease in a greater proportion of the population than had occurred to date – such as previous coronaviruses Sars-CoV and Mers-CoV, which had case fatality rates of around 10 and 35 per cent respectively.

A second scenario was a drug-resistant variant that emerged as a direct result of anti-viral strategies.

Another, unfortunately considered unlikely at least in the short-term, was the virus following an evolutionary trajectory that made it less virulent over time.

With 217 million infections and some 4.7 million deaths to date, Baker said Sars-CoV-2 had already shown the world what it was capable of.

“And when we put barriers in the way of the virus, of course, we create selective pressure favouring variants,” he said.

“Like influenza, it has those two evolutionary trajectories of drift and shift – gradually accumulating mutations over time that give it a slight edge.”

That the virus would grow infectious and resistant against vaccines was predictable, he said – but much harder to forecast was what’s called antigenic shift.

“That’s where influenza can come back as a pandemic because it looks like a new virus to our immune system, and suddenly, we’re not immune to it,” he said.

“We already know this virus does recombination events – and it’s likely that it could recombine with other lineages of Covid-19.

“And then, sooner or later, you’re going to get a variant that has all of the worst attributes that can be picked up from other variants. It becomes more infectious, more vaccine resistant and potentially more lethal.”

Baker said it was also possible the virus could pick up troublesome elements from the other four types of coronavirus circulating as common cold viruses, or even from the hundreds of coronaviruses in the animal world.

“Because we’re now exposing animal species to the onslaught on this virus, it’s possible we could see more cases of reverse zoonosis.”

Already observed in rare cases – including mink, felines and rodents – this could involve the virus infecting animals and then crossing back into humans.

“It could lead to something really quite foreign – and we may end up with little protection from the vaccine.”

Because of this threat, vaccine-makers are locked in an arms race with the fast-evolving virus – and it’s likely that booster shots will be needed to combat variants as they emerge.

As it stood, two doses of the Pfizer vaccine gave 88 per cent effectiveness against infection with Delta – and 96 per cent protection against severe illness.

Protecting NZ

“All of this makes me think that we shouldn’t give up on the elimination strategy too quickly and just say, ‘let’s live with the virus’,” Baker said.

In a commentary published this week, Baker and fellow Otago public health experts said that sticking with elimination could protect the country from new variants, all while keeping death and illness rates row and shielding the health system and our economy.

“More broadly, continuing the elimination strategy in the medium term allows New Zealand to keep its option open,” the researchers wrote.

Contrary to remarks that Delta couldn’t be quashed, they argued that South Australia, Queensland, Taiwan, Hong Kong, China and Singapore had already proven Delta outbreaks were controllable – although it demanded “extensive and swiftly” implemented public health interventions.

The ongoing need for public health controls was also driven home by a new modelling study that found reopening borders without any measures could lead to more than 11,000 hospitalisations – and more than 1000 deaths – within a timeframe of only two years.

And that would be the case even if we managed to vaccinate nine in 10 of all Kiwis – an unlikely probability.

“High vaccination uptake will significantly reduce infections and serious complications, but population-level immunity will be limited by the lower efficacy of current vaccines against infection and transmission of the Delta variant,” the Otago researchers said.

Therefore, they added, New Zealand should look at strengthening alert levels to better deal with Delta outbreaks – and also consider other system improvements, like better border security and a dedicated quarantine facility.

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