New Covid variant BA.5 has a growth advantage, becoming the most common strain and driving third Omicron wave

Daily Covid infections have soared by more than a third since the Jubilee celebrations kicked off, driven by the street parties and other events held to mark the occasion.

But there’s another increasingly important factor behind the increase – the growing prevalence of the BA.5 subvariant of Omicron and, to a slightly lesser extent, the closely-related BA.4 lineage.

Scientists believe that BA.5 is now growing so fast that in the last few days it has overtaken BA.2, which until recently represented the vast majority of UK Covid cases, to be the most prevalent variant in the country.

And while there is still much uncertainty about the danger these new subvariants pose there is no doubt that it has some kind of “growth advantage” over BA.2 – whether it’s due to being intrinsically more infectious, better able to evade immunity built up from vaccination or prior infection, or a combination.

One key study from Japan paints a concerning picture, suggesting that BA.4 and BA.5 are even more contagious than BA.2, more severe (although much less so than the Delta or Alpha variants) and better at evading both kinds of immunity .

This means that while the recent sharp rate of increase in new cases is not expected to continue (with the Jubilee-related increases likely to run out of steam about a fortnight after the event, which is tomorrow) – cases are unlikely to come down much , if at all, before inevitably rising again in Autumn, experts say.

Daily symptomatic infections have risen by 34 per cent since Wednesday June 1, the day before the long Jubilee weekend, from 114,030 to 152,868 on Sunday, according to the ZOE Covid study app.

Professor Francois Balloux, director of the University College London Genetics Institute, has been following the evolution of Covid closely.

“It looks like BA.5 (and its daughter lineage BA.5.1, which is a single mutation away) might now be the most common SARS-CoV-2 lineage in the UK,” he said.

On June 7, the last date for which data is available, BA.5 and 5.1, which he lumps together because of their near-identical nature, accounted for 17 per cent of cases and BA.4 a further 11 per cent. BA.2, meanwhile, was at 30 per cent.

But based on the way things were going – and what we know so far about the new subvariants – he expects things have “changed a fair bit over the last week”, with BA.5 now the most common lineage – although it may not be the ‘dominant’ strain yet as it is probably still below 50 per cent of the total.

“I suspect there is a spike underway in the UK primarily driven by the spread of BA.5/BA.5.1. Based on what happened in South Africa [where it originated], cases, hospitalizations and deaths should in principle remain well below what we experienced during the earlier BA.2 wave. That said, with a bit of bad luck we might still reach around 1,000 hospitalisation/day by the end of the month [about double what they are now in the UK],” Professor Balloux said.

The latest data from the Office for National Statistics, relating to the week ending June 2nd and released on Friday, also points to a sharp rise in BA.4 and BA.5.

“There were early signs of a possible increase in the percentage of people testing positive for coronavirus in England and Northern Ireland likely caused by increases in infections compatible with Omicron variants BA.4 and BA.5; the trends were uncertain in Wales and Scotland,” said Sarah Crofts, head of analytical outputs on the ONS Covid Infection Survey.

The Japanese study conducted a series of experiments involving human cells in the lab and mice, which were injected with the spike protein of the virus, that enables the virus to penetrate the cell.

“Our study finds that transmissibility – more precisely, effective reproduction (R) number -, ‘intrinsic’ pathogenicity [capacity to cause disease]and immune evasion, of BA.4/5 are higher than those of BA.2,” said Professor Kei Sato, who runs the Sato lab at Tokyo University, which led the research.

He says the study also provides a timely reminder that viruses can evolve to become more severe – pathogenic – as well as less, as time goes on.

“Our data suggest that viruses do not necessarily evolve to attenuate their pathogenicity. Therefore, we should continue to rapidly evaluate newly emerging variants. Viral evolution will continue, it never ends,” he said.

The study, published on the bioRxiv preprint server ahead of peer-review because of its timely nature also found that, as with Delta – and unlike BA.2 – BA.4 and BA.5 developed more in the lungs and less in the throat .

“It’s clear that BA.4 and BA.5 have got a growth advantage over BA.2 because they’re replacing it. That’s probably most due to immune evasion,” said Steve Griffin, of Leeds University, who was not involved in the study.

He said the study was “valid and concerning” although he would like to see the “full length” of the viruses examined, rather than just the spike protein.

“Mutations in the spike protein do seem to be changing and that could correlate with severity but I think we should wait to see what the full infectious virus does before we draw too many conclusions about it,” he said.

But if these results are confirmed it would suggest a shift in the growth back to the lower lung “which could potentially increase pathogenesis [severity],” he said.

Another new study, from the UK, suggests that, when it comes to vaccines, the protection they confer is similar for BA.1, BA.2, BA.5 and BA.5.

Meanwhile, a previous BA.2 infection gives better protection against reinfection by BA.4 and 5 than a previous infection by BA.1, although in both cases that protection is weak.

This means people who have had Covid in the past few months will be better protected than those who had it in the weeks before or after Christmas – both because they are more likely to have had BA.2 and because their immunity has waned less. (The initial Omicron virus, BA.1 was dominant around Christmas time before gradually giving way to the BA.2 lineage).

More encouragingly, the study found that a vaccination followed by any Omicron infection gives good protection against reinfection from BA.4, BA.5 and other new variants – although that protection is known to wane over time (from three months afterwards and particularly after six months).

“We find sera [blood] collected post-vaccination have a similar ability to neutralize BA.1, BA.2 and BA.4/BA.5,” according to the study, published as a preprint ahead of peer-review on the bioRxiv server, involving researchers from institutions such as Imperial College London, Oxford University and Glasgow University.

“In contrast, in the absence of vaccination, prior infection with BA.2 or, in particular, BA.1 results in an antibody response that neutralizes BA.4/BA.5 poorly. Breakthrough’ infection with Omicron in vaccinees leads to broad neutralizing response against the new variants.”

The study also provides further evidence that BA.2 is more similar to BA.4 and BA.5 than either are to BA.1.

“These data suggest that BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2,” the study found.

Professor Christina Pagel, of University College London, who was not involved in the studies, said: “It does seem that BA.4/5 have evolved more to pick up more of the way Delta got into cells than BA.1 and BA. 2 did – which means they may cause more lung disease again after Omicron has been causing less.

“But they’re also running into a population that is more boosted and has had more previous infections, so you have these two things going in opposite directions.”

“The big lesson from BA.4 and 5 is that there isn’t this inevitable evolution to mildness, that doesn’t seem to be happening. It’s just evolving in a way that it can infect people, which may mean that it is more mild or it may mean it’s less mild.”

“The problem in the UK is that we are going to be the first country to have a BA.4/5 wave, having had two other Omicron waves and not one. So we’re the test case.”

“We had a BA.1 wave and a BA.2 wave – whereas Portugal and South Africa [where BA.4/5 began] only really had a BA.1 wave before. So the question is, does having a BA.2 wave give you more protection against BA.4/5 wave. Is there an additional immunity benefit from having BA.2?

We’re definitely going to have another Omicron wave – more cases, more admissions and eventually more deaths. The likelihood is they’ll be lower peaks than we had in March and January. But there are so many different aspects I don’t know how it’s all going to play out.”

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