Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: National Institute of Allergy and Infectious Diseases, NIH

New Covid-19 variant XE may be more transmissible – Expert Reaction

The World Health Organization is warning of a new Covid-19 variant that may be more transmissible than Omicron BA.2.

XE is potentially 10 per cent more transmissible than BA.2, and was first detected in the UK in January. Director-General of Health Ashley Bloomfield is planning for wider genomic sequencing to pick up the variant if it arrives in New Zealand.

The SMC asked experts to comment on the new variant XE. 

Dr Jemma Geoghegan, Virologist, Senior Lecturer, University of Otago, comments:

“Viruses often undergo a process called recombination. Recombinant viruses can emerge when two or more variants of a virus infect the same person (and the same cell) at the same time, allowing the variants to interact during replication. This can result in a mix up of their genetic material, forming new virus combinations. SARS-CoV-2 has been recombining throughout this pandemic but it is perhaps becoming more common, or at least easier to spot, due to the very high prevalence of cases.

“Several recombinant strains have been detected in recent months. In fact, there are now 17 recombinant variants classified. These are a combination of Delta and Omicron, as well as a mix of the Omicron subvariants. One recombinant virus variant in particular, called XE, has sparked fresh concerns.

“The XE recombinant variant was first detected in the UK in mid-January. It is a recombinant of the two most common Omicron subvariants: BA.1 and BA.2. That is, it contains genetic material from both of these subvariants. Around 700 genomes have been assigned to XE so far.

“Modelling by scientists predicts that XE has a slight (5-10%) growth advantage over BA.2, which makes it the most transmissible subvariant of Omicron identified to date.

“XE has not been assigned its own Greek letter yet. For the moment, it belongs to Omicron until significant differences in transmission and disease characteristics, including severity, are identified. So far there is not enough evidence to draw conclusions about the transmissibility, severity or immune evasion properties of XE. It is quite likely this recombinant would possess similar disease characteristics to its ‘parents’, BA.1 and BA.2.

“None of the 17 recombinant variants already classified have been detected in New Zealand yet, nor has there been any new recombinant events identified here. The WHO urges the need for ongoing genomic surveillance worldwide so new variants and recombinants can be quickly identified.”

No conflict of interest declared.

Dr David Welch, Senior Lecturer, Centre for Computational Evolution and School of Computer Science, University of Auckland, comments:

What is the XE variant?

“The interesting thing about the XE variant and what’s different from previous variants like Omicron or Delta, is that it’s a recombinant. That means there’s someone out there who has been infected by two variants of COVID at the same time – in this case the Omicron sub-variants BA.1 and BA.2. When the viruses replicated, it made an error in the copying process, and copied one bit from one variant and another bit from another variant. So you get this hybrid – sort of like how you’ve got two parents, and you get some of one parent’s genetic material, and some of the other parent’s genetic material.”

The WHO says it may be 10% more transmissible, does this mean it will outcompete other variants?

“For any new variant to propagate, it needs to be at least as transmissible as any other variant that’s out there. But sometimes a variant might have a similar level of transmission, but it takes hold through super spreading events, or just by chance in a particular city, and so it initially appears to have a transmission advantage. A transmission advantage around 10% is pretty low, compared to the jumps we’ve seen with other variants being about 50-70% more transmissible. At this stage, I think this could be down to a random event, or it’s maybe got a very slight transmission advantage. So I’m not too worried about it at this point.”

NZ has had both BA.1 and BA.2 circulating since the beginning of the Omicron outbreak, what does this mean for how XE will affect us?

“A recombinant basically inherits its properties from its parents. Since XE is the child of BA.1 and BA.2, it’s probably similar in terms of its virulence (how sick it makes people) and its immunogenic properties (the way our immune systems respond to it). The spike protein in XE – which is the first thing that our immune system sees – is from BA.2, which is now the dominant variant in New Zealand. So I would expect anyone who has recently been infected with BA.2, would have some immune protection against XE.”

Should we be less worried about this variant because the WHO hasn’t given it a Greek alphabet name yet?

“We shouldn’t be too concerned about XE at this time. The WHO have not promoted it to a Variant of Concern and given it a Greek letter for good reason. On the face of it, I do not expect this variant to rapidly spread around the world like Delta or Omicron did. That is based on looking at the “parent” variant of XE: while BA.1 and BA.2 are quite far apart in terms of mutations, the way they escape our immunity is somewhat similar. If it were a cross, say, between Delta and BA.2 and were spreading quickly I might be more worried because BA.2 can escape immunity, and Delta is very virulent. Luckily we haven’t seen a recombinant like that yet.”

Has the shift away from PCR testing and comprehensive genome sequencing left us vulnerable to XE spreading undetected?

“Our sequencing effort is below par at the moment because not enough cases are being sent of sequencing. We’re not getting a detailed picture of what is happening across the country as sequencing numbers are uneven across DHBs. If XE arrives and it isn’t picked up at the border, then it could be many weeks before we detect it at all. The other point is there’s a lot of BA.1 and BA.2 out there and a lot of infection here in New Zealand, so it’s quite possible we’ve produced our own recombinant variant that could be circulating.

“Nearly all the information we have about XE is coming from the UK which has had amazing surveillance systems, and has given us early warning about all sorts of things. However they have really dialed back that system now. And we’ve been sort of piggybacking on that to some extent. So there is an increased need for us to pick up some of the slack and do more of the work ourselves.”

Conflict of interest statement: David is providing analysis to the Ministry of Health on genomic testing of cases.