The SARS-CoV2 virus just won’t give up. As the northern hemisphere heads into its third pandemic winter, experts say the continued evolution of Omicron’s sub-variants indicates a fresh wave is coming, but no one knows which variant will fuel it.

Scientists have catalogued 390 Omicron lineages and 48 recombinants of the virus – which occur when at least two variants co-infect the same person, allowing them to ‘exchange notes’ and evolve. The sheer number of Omicron strains circulating makes predictions complicated.

“We’re having trouble isolating which of the omicron sub-variants will have a growth advantage and will take over in dominating the spread,” WHO Senior Emergency Officer Dr Catherine Smallwood explained at a press conference last week. “Some variants like BQ.1 have been noted as potentially accelerated, but we’re not sure yet how this is going to pan out in the longer term.”

The variety of offshoots also creates the possibility of a ‘double wave’ in some places if two successive variants with different immune-dodging characteristics succeed each other.

“Looking at all the data, it seems a sizable new infection wave is certain to come,” Tom Wenseleers, an evolutionary biologist at the Catholic University of Leuven told Nature.

Subvariant surges not causing hospitalization spikes – for now

There is some good news: early signs show that though the BA.4, BA.5, BQ.1.1 and XBB subvariants are able to break through immune protections and resist certain treatments, they do not appear to be causing increases in hospitalizations.

“An encouraging sign for one of – if not the most – immune evasive new variants XBB: it is dominant in India and Bangladesh without a rise in cases or deaths to date,” said Eric Topol, founder and director of Scripps Research.

Similar findings have come out of South Africa, where the Africa Health Research Institute in Durban conducted studies on the BA.4 and BA.5 sub-lineages. The team, led by virologist Alex Sigal, found that while these Omicron families possess strong enough immune-dodging mechanisms to lead to an infection wave, they are “not likely to cause much more severe disease than the previous waves, especially in vaccinated people.”

The World Health Organization’s (WHO) Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE), which released a statement singling out BQ.1 and XBB as key variants of concern on Thursday, issued a similar analysis.

“While we are looking at a vast genetic diversity of Omicron sublineages, they currently display similar clinical outcomes, but with differences in immune escape potential,” TAG-VE’s expert panel found. “So far there is no epidemiological evidence that these sublineages will be of substantially greater risk compared to other Omicron sublineages.”

World trending in the right direction – but surprises could be around the corner

The question lingering on the mind of many experts is whether the varying properties of subvariants mean infection by one will provide immunity from others – a key determinant of whether double waves will hit.

A team at Peking University in Beijing, led by Yunglong Richard Cao, has been studying the variants’ immune-evading capacities. “I have a feeling that if you’re infected with BQ.1, you might have some protection against XBB,” he told Nature. “We don’t have data yet.”

Experts warn not to rule out more surprises from the virus. With Delta still circulating in the background, the deadlier variant could return to the fore. 

“The virus has surprised us more than once,” said Dr Hans Kluge, WHO Europe Regional Director. “We are much better prepared, and the fall surge has not led to previous ICU admission or severe disease levels, but forecasting remains tricky.” 

Reports emerged this week of yet another subvariant, BA.5.2.6 taking hold in Ukraine. The dire conditions occasioned by Russia’s invasion of the country have made it conducive ground for viral spread, and reporting since the start of the conflict has dropped off a cliff. 

Little is known about the true state of play on the ground – nor which subvariant will take over next. 

Image Credits: Nature, Stuart Turville.