Commentary: Can we be cautiously optimistic about new Omicron XE variant?

LEEDS, England: As the COVID-19 pandemic has progressed, we’ve repeatedly seen the arrival of new viral variants. Variants of concern, such as Delta and Omicron, are versions of SARS-CoV-2 (the virus that causes COVID-19) which have acquired mutations. 

These mutations can provide SARS-CoV-2 with a genetic advantage. For example, Delta is linked to more serious illness than the original Wuhan strain, while Omicron is more infectious.

Now we are seeing recombinant variants such as Omicron XE. These are not viruses that have picked up a few mutations. Instead, they are viruses containing a combination of genetic material from multiple variants, producing a new version of the SARS-CoV-2 virus.

So far there have been at least 1,179 cases of Omicron XE identified in the United Kingdom, according to the most recent update from the UK Health Security Agency published on Friday (Apr 8). The majority of these cases have been in the south and east of England.

There have also been reports of a handful of cases elsewhere around the world, likely due to international travel.

So how worried should we be about Omicron XE? While we don’t know a lot about it yet, what we do know doesn’t suggest there’s cause for serious concern.

RECOMBINANT VARIANTS LIKE OMICRON XE, DELTACRON

When viruses replicate, they sometimes make mistakes in their genetic code, leading to individual mutations. Often, these mutations don’t result in any change to the structure of the virus – termed “silent mutations”.

Some mutations, however, can confer an advantage. For example, mutations that occur in the spike protein (the part responsible for infecting our cells) can make the virus more transmissible than previous variants. We’ve seen repeated mutations in the spike protein produce variants of concern.

Recombination is a different process, whereby two different variants infect the same cell, in the same person, at the same time.  From there, they can combine their genetic material, resulting in a virus that possesses a mix of genes from both infecting “parent” viruses. This recombinant variant may then spread to other people – as has been the case with Omicron XE.

In fact, multiple recombinant variants have been identified globally by PANGOLIN (the SARS-CoV-2 lineage surveillance carried out by the COVID-19 genetics UK consortium). At least three of these – XD, XE and XF – have been detected in the UK.

Some recombinants, such as XD and XF, are combinations of the Delta variant with Omicron lineages. You might have heard of these hybrids, which have been dubbed “Deltacron”. XE, however, is a combination of two Omicron strains: BA.1 and BA.2.

RAPID SIGNIFICANT CHANGES CAN OFFER ADVANTAGE

Genetic recombination of viruses is not a new phenomenon. It occurs regularly with viruses such as influenza and HIV. Indeed, one of the proposed origins of the original Wuhan SARS-CoV-2 virus is from a recombination event in bats.

From an evolutionary perspective, recombination offers viruses an advantage, as it allows more rapid and significant changes to the virus, compared with the slower process of acquiring mutations through errors in replication. 

Recombinant viruses can exhibit marked changes in their behaviour, such as increased infectiousness, evasion of our existing immunity to the virus or resistance to drugs. Much like error-based mutation, however, some recombinant viruses show no apparent differences from their parent viruses.

We know that Omicron XE has the majority of its genetic information, including the spike protein, from the Omicron sub-variant BA.2, which is the predominant variant in the UK at the moment. 

HOW OMICRON XE COMPARES TO PREVIOUS VARIANTS

It is likely, therefore, that the characteristics of Omicron XE (such as transmissibility, the severity of disease and vaccine efficacy) are similar to those of BA.2. But it’s prudent that scientists continue to monitor and study Omicron XE, as it is a genetically distinct virus from its parents.

Initial data for the Omicron XE variant suggests that the growth rate (that is, the proportion of new infections in the population) is slightly higher than that of Omicron BA.2. However, because there are only a small number of infections with XE at present, the data we have on this is limited and it’s difficult to draw solid conclusions for now.

Reassuringly, we know that BA.2 is no more severe than BA.1 and that Omicron variants overall tend to cause less severe disease than previous SARS-CoV-2 variants. But they are highly infectious.

The need for updated vaccines is becoming ever-pressing since all current vaccines are based on the original Wuhan strain. Data has shown that the more changes in the spike protein subsequent variants have acquired, the less effective our current vaccines are at preventing infection. That said, vaccines are still very effective at preventing severe disease or death from COVID-19.

Of course, we need more research to understand the characteristics of this new Omicron XE strain. But it appears, at present, to be very similar to the currently circulating strains of SARS-CoV-2. As we well know, it’s not the first variant of the virus, and it’s highly unlikely to be the last.

Grace C Roberts is a Research Fellow in Virology at the University of Leeds. This commentary first appeared in The Conversation.