When 2 coronavirus variants meet inside 1 person, a Frankenstein hybrid can be born

On February 16, Scott Nguyen went hunting. And what he found is a bit surprising: a coronavirus variant that looks like a Frankenstein virus. It has the head of the omicron variant stuck onto the body of the delta variant.

Officially, Scott Nguyen is a bioinformatician at the Public Health Laboratory in Washington, D.C. He tracks emerging coronavirus variants around the city.

But on the side, Nguyen and a handful of scientists around the world have an intriguing hobby: "We're variant hunters," he says. "I think that's a pretty cool way to describe it."

Nguyen and other variant hunters search through millions of SARS-CoV-2 genome sequences in a massive database, called GISAID, looking to uncover strains that could shift the course of the pandemic – or simply give scientists a better understanding for how the virus evolves.

For instance, back in November one variant hunter found "a very weird set of ...mutations coming from a variant in South Africa," Nguyen says. "That became omicron."

Then early one morning in February, Nguyen detected not simply another variant but a whole new class of variants: variants that mix together parts of delta and omicron. And not just any parts, randomly put together. In some instances, the virus seems to be optimizing the combinations – picking the best traits from each for infectiousness and immune evasion.

'Deltacron' — an omicron spike protein and a delta body

Specifically, Nguyen found a variant that's mostly delta but contains the spike protein of omicron – the tiny studs on the surface of the virus that initiate infection. "So a good chunk of the virus' spike protein is omicron but the body of the virus is still delta," Nguyen says. "So yes, that's the best way to describe it."

So far, this variant, called XD, is rare. So, scientists have detected it in only France, Denmark, Belgium, the Netherlands and Germany. But there are likely many of these deltracrons out there. Scientists in San Mateo, California, have already found a handful of them in the U.S. At least one has emerged in the U.K. and Brazil.

Health officials, including those at the World Health Organization, are watching these hybrid variants closely. Because they demonstrate how the virus can take its most successful parts and combine them quickly into a supervirus. This process is called recombination, and it's how dangerous strains of flu are made.

"So very often recombination is the way in which we get pandemics of influenza. ," Dr. Mike Ryan with the World Health Organization said on Friday. "So we have to be very cautious ... we have to watch these recombinant events very, very closely."

For instance, omicron's spike protein is especially apt at hiding the virus from our immune system, especially our antibodies. And so the XD variant is essentially the delta variant wearing omicron's invisibility cloak.

"From the variant's perspective, it has the best of worlds," Nguyen says. ""It's surprising that the virus can really do this, and do it very well, as well.

How a Frankenstein hybrid is born

So how does the virus do this? How does it create these Frankenstein hybrids?

For starters, a person has to catch both omicron and delta at the same time, says Shishi Luo, a bioinformatician at the genomics company Helix. "So a person has to be exposed to both variants in a short enough time frame so that they have both of them in this system."

Luo and her colleagues recently analyzed samples from nearly 30,000 Americans infected with SARS-CoV-2 during the rise of omicron in this country, from November until February. They found 20 people co-infected with both delta and omicron. In other words, they were infected twice.

"Omicron happened around Christmas and New Year, when there were many social gatherings," Luo explains. "So you can imagine, you go to one social gathering and got exposed to delta, and then you go to a different social gathering, and you catch omicron."

If both variants manage to infect the same cell, at the same time, then the virus can end up doing recombination, Luo says. In essence, during replication, one variant steals a chunk of genes from another variant. So the delta variant, in way, plagiarized part of omicron's genetic code.

"If you're writing a document, you can have typos where you change a single letter," Luo says. "But you can also copy and paste and move big chunks of text. That's recombination, where one variant, in this case delta, takes a big chunk of text from omicron."

Grabbing chunks of code instead of just single letters makes the virus more malleable or flexible, Luo says, so it can quickly evolve new variants, including ones that can evade our immune protection. "It just shows how SARS-CoV-2 has many tools in its kit for changing itself."

Recombination could key to the past and future of SARS-CoV-2

Scientists are just starting to understand how important recombination is for SARS-CoV-2 evolution. "It's been known that coronaviruses, in general, have a lot of recombination. For SARS-CoV-2, this is the first time we've seen so much evidence that it's happening," she adds.

In fact, recombination may be the reason SARS-CoV-2 exists in the first place. Last month, scientists at the University of Glasgow published a study in which they speculate about the origins of SARS-CoV-2. Their analysis suggests an animal in the Wuhan seafood market could have been co-infected with two coronaviruses at the same time – and that these two viruses recombined, just like omicron and delta are doing right now, to generate the initial version.

"You know, early on in the pandemic, we were all expecting SARS-CoV-2 to not mutate too much," Scott Nguyen says. "But this virus has surprised us at every corner. So I think these recombinant variants provide some interesting clues to how this virus is going to evolve next" – and just how quickly the next variant of concern may appear.

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