How the splintering of Omicron could shape Covid’s next phase

The United States is in a (relative) Covid-19 lull, with cases and hospitalizations declining as the wave driven by the BA.5 line of the Omicron variant recedes. But as if we needed an omen an expected autumn and winter waveCovid is on the rise in some European countries.

What’s different, at least for now, is that there’s no variant driving the wave. Rather, scientists are tracking a flock of new forms of Omicron that contend with each other as they compete to become the next dominant strain. Scientists are monitoring more than 300 sublineages of Omicron, World Health Organization officials said this week.

To get a sense of what’s happening with the development of the SARS-CoV-2 virus, STAT spoke up tom peacockVirologist at Imperial College London.

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The strains virologists are pursuing — from BA.2.75.2 to BQ.1.1 to XBB and beyond (“The names are getting more ridiculous,” Peacock said) — are themselves descendants of earlier forms of Omicron, such as BA.2 and B.A. 5. It is an example of how the development of the coronavirus has developed since the emergence of Omicron almost a year ago rather the “drift” seen in influenza, rather than the earlier succession of very different variants, from alpha through delta to the original omicron.

“It’s a bit like what we’d expect after a few years of flu, but pushed into about three months with SARS-CoV-2,” Peacock said.

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But even as the Omicron lineages continue to fragment, scientists have found that the different sublineages pick up some of the same mutations — what’s called “convergent evolution.” This pattern suggests that these mutations confer an evolutionary advantage, one that would allow the virus to spread further among people who have different layers of protection from vaccination and infection from previous Omicron lineages.

How big and harmful A wave that will drive the emerging sub-variants is unpredictable. In the US, any wave that comes will build to a baseline of what is currently an average of 390 people per day. It’s also not clear if any variant will outperform its cousins ​​or if different combinations will gain a foothold in different parts of the world. (We’ll note here that the new subvariants don’t seem to fully reset the pandemic: the immunity that people have built up through vaccination and infection is likely to continue to provide strong protection against severe outcomes for most, especially if they’ve stayed up-so far with boosters.)

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But the concern about these latest sublines isn’t just that they could send cases skyrocketing again. Some monoclonal antibody treatments have already been rendered useless and had to be given up how the virus evolved. And in some laboratory experiments, the remaining antibody therapies – betelovimab, as well as Evusheld – cannot withstand some of the new variants. (Just on Monday, the Food and Drug Administration warned that Evusheld, the given to immunocompromised people to bolster their protection as pre-exposure therapy cannot neutralize certain SARS-2 variants.) This could make people at high risk of severe Covid even more vulnerable.

Peacock added a note: While it’s possible that the future SARS-2 strains we’ll be looking at continued to be Omicron-derived, another Omicron-like event could occur. That means a variant from a distant part of the SARS-2 family tree could suddenly emerge and outstrip everything else in the landscape, just like that the original Omicron did it last year around Thanksgiving.

“We’re also approaching Omicron’s one-year anniversary, so something else might come along and just make everything else die out,” Peacock said. “We should never forget that SARS-CoV-2 did this once and can absolutely do it again. Everyone looks at these tiny changes in all these sublines and suddenly pi comes through and torpedoes the whole lot,” Peacock said, referring to the next letter in the Greek alphabet that would presumably be given to the next major variant.

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Below are excerpts from STAT’s conversation with Peacock, edited slightly for clarity.

In general, what is currently happening with the development of SARS-2?

We’re seeing a fairly unprecedented amount of convergent evolution – not for other viruses, but for SARS-CoV-2. In other words, although things started in different places – some BA.2, some BA.5 – everything goes back in the same direction. They get the same mutations, which implies that there’s a very strong selective pressure in the environment right now, which of course is people’s immunity, or that’s what everyone assumes.

One thing people may have heard when new variants pop up is that they’re the “most immune-evasive yet.” By definition not any variant that shows up in our current immune landscape and is spreading well to have to be able to evade all that immunity to circulate? Isn’t that what we should expect?

Yes, it is absolutely expected. This is how drift occurs.

If expected, is it cause for concern? Aside from the impact on therapies, is there any idea what impact these sub-lines might have on the effectiveness of vaccines? Countries in Europe and the US introduce these bivalent boosters that make up Omicron, but earlier forms of Omicron.

It’s very difficult to say because we don’t really know what the vaccine’s effectiveness will be against a fully matched virus. This data takes a while. But it will likely be similar to what it always has been as there will be some drop in protection against infection and symptomatic disease because you have a discrepancy now. But things like serious illness and death will hold up much better, and there will be a much less dramatic drop, and maybe not even a big drop.

Is it surprising that despite all the evolution this virus has gone through, it still finds room to pick up new mutations and is still able to infect, replicate and things like that? I remember hearing experts talking earlier in the pandemic about how there was only a certain number of mutations a virus could tolerate before losing function. Are we just not there yet?

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People have gone back and looked at some of the seasonal coronaviruses and you see they have a high tolerance for mutations and SARS-CoV-2 clearly shows a high tolerance as well.

A resurgence in cases is currently being seen in parts of Europe at least, but it’s not like there’s a brand new variant driving it. So what’s happening now with the transmission, and what might happen as these new Snowball and BA.5 variants continue to go backwards?

People say that maybe some of the variants are less well distributed than some of the new sublineages, but still have some antigenic mutations – such as BA.4.6, BF.7, which are quite high in some European countries – you may be the vanguard of this wave of variants that we’ll get over the winter, but the really bad guys are still at a percentage point or a few percentage points in prevalence. So you have the first ones to be replaced when the wave comes through with these nastier ones that are currently at a lower prevalence. We could end up with a mix, and different countries end up with different mixes.

Add to that schools that are declining across Europe, a sudden cold spell – so maybe there’s some seasonality – and dwindling immunity. It’s just all at once, and it’s unclear what each post is. But if variants aren’t driving it now, we think they will be in a couple of weeks.

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