Stopping the next major variant of the coronavirus involves knowing where it might come from.
With Omicron, those answers are still a mystery: how did a variant that looked so different from all of its older cousins appear so suddenly? How to explain this amount of mutations, many of which were rarely seen in variants of interest?
“When this sequence of viruses started to emerge, it was very difficult for me to imagine that it would take off,” said Emory University virologist Mehul Suthar.
The alphanumeric soup also revealed BA.2, a faster-spreading subtype of Omicron that has become dominant in the United States.
Viruses change all the time, often in ways that really hurt your chances of survival. But every now and then, these mutations can work in the virus’s favor.
mutations
The virus you sneeze or cough on may be slightly different from the one you were infected with.
That’s because viruses mutate — especially when their genetic code is made up of RNA, a close cousin of our DNA.
“As the virus reproduces, there are errors in the reproduction of its code,” explained Mike Ryan, executive director of the health emergencies program at the World Health Organization (WHO), in a March briefing. “Most of these errors result in a virus that is not competent or simply disappears.”
But rarely, these accidents can give the virus an edge. Maybe it becomes more contagious. Or maybe it becomes better at evading our immunity.
Sarah Cobey, an associate professor of ecology and evolution at the University of Chicago, explained in an opinion piece in the New York Times this week that the transmissibility of the coronavirus will hit a ceiling — eventually. However, it likely won’t stop evolving in ways that bypass our immune response.
But not all mutations happen in the same way.
“Before Omicron, I think most people in the field would say that we would see immune escape through the accumulation of these mutations one by one,” Cobey told CNN.
Over time and over hundreds of infections, circulating viruses move further and further away from their ancestors in the evolutionary tree. It is a process known as antigenic drift.
However, while this may explain the variants that appear closest in the evolutionary tree – such as Ômicron and its branch BA.2 – it does not explain how Ômicron appeared in the first place.
“Omicron took everyone by surprise,” Cobey said.
Marietjie Venter, a professor in the Department of Medical Virology at the University of Pretoria in South Africa, said it is unlikely that a “slow change” led to Omicron.
This would mean that the virus gradually evolved in a population that was not being monitored. And South Africa, where many of the first Omicron samples were identified, has a good surveillance program, she said.
So it would have been difficult for a variant like Omicron to slowly pull away. Instead, his appearance seemed curiously abrupt.
“Delta almost disappeared and all of a sudden we saw Omicron that was completely different,” said Venter.
antigenic change
In some cases, viruses do not spread; they change.
The “antigenic shift” is a more dramatic change that can happen, for example, when viruses in animals reach humans or when two strains infect the same person and exchange genes.
Examples of the latter include rare cases of a hybrid virus containing stretches of the Delta and Omicron genes.
Researchers at Helix, a company whose Covid-19 tests helped screen for several variants, identified a cluster of combined Delta-Omicron infections in the US among nearly 30,000 coronavirus samples from late November to mid-February, when both variants were circulating.
From these samples, the researchers identified 20 cases in which people were infected with both variants at the same time. One of these samples showed some evidence that the variants exchanged genes, albeit at low levels. In addition, the researchers found two unrelated cases whose infections originated from hybrid viruses.
“Currently, there is no evidence that the two Delta-Omicron recombinant viruses identified are more transmissible between hosts compared to the circulating Omicron lineages,” the researchers wrote.
“We are not calling this Deltacron,” Maria Van Kerkhove, WHO technical lead on Covid-19, said at the March briefing. “That’s not terminology we’re using.”
At the time, Van Kerkhove said that this combination appeared to be circulating “at very low levels,” but she made the caveat that we should be testing more to get a clearer picture of its prevalence and spread — or lack thereof.
Still, the ability to switch genes has spurred the resurgence of several viruses, most notably the flu.
The genetic material of the flu is made up of several segments of RNA that can move back and forth when two viruses co-infect the same cell. This is known as rearrangement.
But the coronavirus “can actually do something that’s even harder to understand,” Cobey explained, referring to a gene-swapping process called recombination.
Unlike the flu, the coronavirus has a long strand of RNA as its genetic code. When two strains infect the same cell, its replication machinery may occasionally jump from one strain to another. This creates random “breakpoints” in your genetic code that are stitched together.
While the flu shuffles entire cards, in a way, each coronavirus has just one card — but it’s extra long and can be cut and pasted in a variety of ways.
That means the virus has “a lot more evolutionary space that it can be exploited quickly,” Cobey said.
In the editorial, she and her coauthors describe how we may have only seen the tip of the iceberg when it comes to the number of possible mutations the virus can sustain and still be able to infect human cells.
While it’s unclear whether recombination is more likely than other pathways to generate the next variant of concern, Cobey said Omicron, in particular, has lit a fire under scientists to understand its origins and the true range of viable mutations.
“This is the kind of divergence that is really difficult to study and anticipate in the lab,” she said.
The Mystery of the Omicron
No explanation seems to fit perfectly into Omicron’s backstory. But experts are circling various theories that could explain its sudden appearance last year.
The most popular view seems to involve an infection that persists for a long time in an immunocompromised person.
“They actually develop antibodies, but they don’t eliminate the virus,” said Venter, who also chairs the WHO’s Scientific Advisory Group on the Origins of New Pathogens.
This gives the virus enough time to accumulate changes, potentially ones that allow it to evade that person’s antibodies and acquire immune resistance.
Another theory is known as reverse zoonosis, Venter added. This refers to humans infecting an animal population, where the virus accumulates new mutations before returning to humans. (In fact, this coronavirus has spread widely across the animal kingdom.)
Staying ahead of the virus isn’t just a matter of anticipating your next move, experts say. It’s about finding ways to avoid threats and ultimately ensuring the durability of our vaccines.
And it’s not just this virus
“Most pathogens that infect us repeatedly are able to do so because they are escaping part of our immunity to previous infection strains,” Cobey said.
“Viral evolution is really a real problem in our lives that we may not formally recognize as such.”
Source: CNN Brasil
