Stopping the next major variant of coronavirus involves knowing where it might come from. With the Ómicron variant, those answers remain a mystery: how did a mutation appear so suddenly that looked so different from all its older cousins? , how to explain its jumble of mutations, many of which had rarely been seen in variants of interest?
“When that virus sequence started to emerge, it was really hard for me to imagine it would take off,” virologist Mehul Suthar, from Emory University, told bCNN. The alphanumeric soup also revealed BA.2, a fastest-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 from time to time, those mutations can work in favor of the virus. The viruses we sneeze or cough up may be slightly different from the ones that infected us. That's because viruses mutate, especially when their genetic code is made of RNA, a close cousin of our DNA. “As the virus reproduces, there are errors in reproducing its code,” Dr. Mike Ryan, executive director of the Health Emergencies Programme of the World Health Organization (WHO), said in a March briefing. “Most of those errors result in a virus that isn't competent or just goes away.”
But on rare occasions, these accidents can give the virus an advantage. Maybe it will become more contagious. Or maybe it becomes better to escape our immunity. Sarah Cobey, 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 eventually hit a roof. However, it will probably not stop evolving in a way that eludes our immune response.
But not all mutations happen the same way. “Before Omicron, I think most people in the countryside would say that we would see an immune escape through the accumulation of these mutations one by one,” Cobey told CNN. Over time and over the course of hundreds of infections, circulating viruses increasingly move away from their ancestors in the evolutionary tree. It's a process known as antigenic drift. However, while this may explain the variants that appear closer in the evolutionary tree, such as the Omicron and its BA.2 branch, it does not explain how the Omicron appeared in the first place. “The Ómicron variant took everyone by surprise,” Cobey stressed.
Marietjie Venter, a professor in the Department of Medical Virology at the University of Pretoria, in South Africa, said that it is unlikely that a “slow change” would lead to the 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 samples of the Omicron were identified, has a good surveillance program, he said. Therefore, it would have been difficult for a variant such as Ómicron to approach stealthily and slowly. On the other hand, its appearance seemed curiously abrupt. “Delta almost disappeared, and suddenly we saw Ómicron who was completely different,” he added.
In some cases, viruses do not move; they change. “Antigenic change” is a more dramatic change that can occur, for example, when animal viruses reach humans or when two strains infect the same person and exchange genes. Examples of the latter include rare instances of a hybrid virus containing stretches of Delta and Omicron genes.
Researchers at Helix, a company whose COVID-19 tests helped track a number of variants, identified a handful of combined Delta-Omicron infections in the United States among nearly 30,000 samples of coronavirus from late November to mid-February, when both variants were in circulation. Of those samples, the researchers identified 20 cases in which people had been infected with both variants at the same time. One of these samples gave some evidence that the variants had exchanged genes, albeit at low levels. In addition, the researchers found two unrelated cases whose infections originated from hybrid viruses.
“There is currently no evidence that the two identified Delta-Ómicron recombinant viruses are more transmissible between people compared to circulating Omicron lineages,” the researchers wrote. “We won't call this Deltacron,” said Maria Van Kerkhove, WHO's technical director on COVID-19, at the March briefing. “That's not the terminology we're using.” At the time, the expert said that this combination seemed to be circulating “at very low levels”, but cautioned that we should do more testing to get a clearer picture of its prevalence and spread, or lack thereof.
Even so, the ability to exchange genes has driven the resurgence of multiple viruses, mainly influenza. The genetic material of influenza is made up of multiple segments of RNA that can mix back and forth when two viruses co-infect the same cell. This is known as redistribution. But coronavirus “can actually do something that is even harder for us to understand,” Cobey explained, referring to a process of gene exchange called recombination.
Unlike influenza, coronavirus has a long chain of RNA as its genetic code. When two strains infect the same cell, their replication machinery may occasionally jump from one strain to another. This creates random “breakpoints” in your genetic code that come together. While influenza shuffles whole cards, in a sense, each coronavirus has only one card, but it is extra long and can be cut and pasted in a variety of ways.
This means that the virus has “much more evolutionary space that can be explored fairly quickly,” Cobey said. In the opinion piece, she and her co-authors describe how we may have seen only the tip of the iceberg in terms of the number of possible mutations that the virus can withstand and still be able to infect human cells. While it is not clear whether recombination is more likely than other avenues to generate the next variant of concern, Cobey argued that Omicron in particular has lit the fire so that scientists understand its origins and the true extent of viable mutations. “That's the kind of divergence that's really hard to study and anticipate in the lab,” he said.
The mystery of the Ómicron variant
No single explanation seems to fit the Omicron backstory perfectly. But experts are turning to several theories that may explain its sudden appearance last year. The most popular opinion seems to imply an infection that persists for a long time in an immunocompromised person.
“In fact, they develop antibodies, but they don't eliminate the virus,” said Venter, who also chairs the WHO Scientific Advisory Group on the Origins of New Pathogens. This gives the virus plenty of time to build up changes, potentially changes that allow it to bypass that person's antibodies and acquire immune resistance.
Another theory is known as reverse zoonosis, Venter added. This refers to humans who infect an animal population, where the virus accumulates new mutations before returning to humans. In fact, this coronavirus has spread widely among the animal kingdom.
Staying ahead of the virus isn't just a matter of anticipating its next move, experts say. It's about finding ways to avoid threats and ultimately ensure the durability of our vaccines. And it's not just this virus. “Most of the pathogens that repeatedly infect us can do so because they escape part of our immunity to previous infectious strains. Viral evolution is actually a real problem in our lives that we may not formally recognize as such,” Cobey concluded.
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