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In early 2021, scientists in Colombia discovered an alarming new coronavirus variant. This variant, eventually known as Mu, had several troubling mutations that experts believe may help it evade the immune system’s defenses.

In the months that followed, Mu quickly spread throughout Colombia. Causes a new surge in Covid-19 cases. By the end of August, it had been detected in dozens of countries and the World Health Organization had determined it a “kind of interest”.

“Mu was starting to make some noise globally,” said genomic epidemiologist Joseph Fauver of the University of Nebraska Medical Center. a new study on variant.

And then it gushed. Today, the variant has completely disappeared.

For each Delta or Omicron there is a variant of Gamma, Iota or Mu that triggers local fluctuations but never achieves global dominance. Experts say that while understanding Omicron remains a critical public health priority, there are lessons to be learned from these smaller strains.

“There’s no incentive for this virus to stop adapting and evolving,” said molecular epidemiologist Joel Wertheim of the University of California San Diego. And seeing how it has done it in the past will help us prepare for what it might do in the future.”

In addition, the Iranians’ work provided further evidence that America’s international travel bans were not effective, shedding light on surveillance gaps and policy errors and what made the virus successful, suggesting that contagion is more important in the early phase of the pandemic. immunity is better than hijacking.

The research also highlights how important context is; Variants that make an impact in some places can never find a place in others. As a result, it is difficult to predict which variants will become dominant, and knowing about future variants and pathogens will require extensive, near real-time surveillance.

Dr. “We can gain a lot by looking at the viral genomic sequence and saying, ‘This is probably worse than the other,'” Wertheim said. “But the only way to really know is to watch it spread, because there are a lot of potentially dangerous variants that will never take hold.”

Here he is looking at Mu

The coronavirus is constantly changing, and most new variants are never noticed or named. But others are alarming, either because they’re rapidly becoming more common or because their genomes look sinister.

Both were true for Mu, which sprang up in Colombia. “It contained several mutations that people watched very closely,” said Mary Petrone, a genomic epidemiologist at the University of Sydney and author of the new paper Mu. Many of the mutations in the spike protein have been documented in other immune-escaping variants, including Beta and Gamma.

In the new study, yet to be published in a scientific journal, scientists compared Mu’s biological properties with those of Alpha, Beta, Delta, Gamma, and the original virus. Dr. Mu didn’t multiply faster than the other variants, but it was the most immune-evading variant of the group, and more resistant to antibodies than any known variant except Omicron, Fauver said.

By analyzing the genomic sequences of Mu samples collected from all over the world, the researchers reconstructed the spread of the variant. They concluded that Mu likely originated in South America in mid-2020. It then wandered around for months before being spotted.

He said genomic surveillance in many parts of South America was “erratic and incomplete.” Jesse Bloom, a viral evolution specialist at the Fred Hutchinson Cancer Research Center in Seattle. “If there were better surveillance in these areas, it would probably be easier to make a quicker assessment of how worried about Mu would be.”

Mu also presented another challenge. It had a type of mutation known as a frameshift mutation, which is rare in coronavirus samples. Such mutations, Dr. When scientists including Fauver tried to load the Mu sequences into the computer, it was flagged as an error. GISAIDan international repository of viral genomes used to track new variants.

This complexity has caused delays in the public sharing of Mu dramas. The researchers found that the time between collecting a virus sample from a patient and making it public on GISAID was longer for Mu cases than for Delta cases.

Dr. “The genome itself was basically creating artificial surveillance loopholes,” Fauver said. “At least in our experience, it resulted in weeks of not getting the data we would normally try to extract in days.”

(GISAID’s quality control systems are important, the researchers stressed, and the repository solved the problem.)

Combine these surveillance loopholes with Mu’s immune evasion ability and her variant looked ready to take off. But it didn’t. The scientists found that Mu instead spread from South and Central America to other continents, but did not spread widely when it got there. Dr. “This was an indication that this variant is perhaps not as well suited to North American and European populations as we expected,” said Petrone.

This was because Mu found herself in competition with an even more formidable variant: Delta. Delta was not as skilled as Mu at evading antibodies, but was more contagious. Dr. “Eventually, the Delta expanded into a wider area,” Bloom said.

Right variant, right time

Examining successful variants only tells half the story. Dr. “The non-dominant variables are, in a way, negative controls,” Petrone said. “They tell us what isn’t working, and in doing so, they help fill the knowledge gaps around variable relevance.”

Delta outlived Mu as well as several immune-escaped variants, including Beta, Gamma, and Lambda. This model shows that immune evasion alone is not enough to allow a variant to outgrow a highly contagious version of the virus, or at least not in the early stage of the pandemic, where few people have immunity.

But vaccines and multiple waves of infections have changed the immune landscape. A highly immune-avoiding variant should now have more of an advantage, the scientists said, which is likely part of the reason why Omicron has been so successful.

Another recent study found that Gamma, who escaped immunity in New York City, tended to do better In neighborhoods with higher pre-existing immunity, in some cases because they were hit hard in the first wave of Covid. The author of the study, Dr. “We can’t see a new variant in a vacuum because it appears in the shadow of all the variants that came before it,” Wertheim said.

Indeed, the clash of variables in the past reveals that success is highly context dependent. For example, New York City could be the birthplace of the Iota variant. first detected In virus samples collected in November 2020. Dr. “And so it found an early foothold,” Petrone said. Even after the more contagious Alpha variant arrived, Iota remained the city’s dominant variant for months before finally disappearing.

But things turned out differently in Connecticut, where both Iota and Alpha were revealed in January 2021. “Alpha took off and Iota didn’t stand a chance,” he said. a study of variants in two regions.

A similar pattern is already starting to play out in multiple lineages of Omicron. In the United States, a subvariable first identified in New York, BA.2.12.1, took offWhile in South Africa, BA.4 and BA.5 lead a new rise.

This is another reason to study descending variants, said Sarah Otto, an evolutionary biologist at the University of British Columbia. A variant that is poorly matched for a particular time and place may appear elsewhere. Indeed, it may have been Mu’s misfortune that it came to light too soon. “There might not have been enough people with immunity to really give this variant a boost.” said.

But the next variant of the concern could be a descendant of an immunity-escaped lineage that never quite took hold, or something like that, he said.

Looking at previous variables can give you insight into what works and what doesn’t include them. The new Gamma study provides further evidence: international travel bansIt is unlikely that a variant will prevent its global spread, at least because the United States has implemented them.

Gamma was first described in Brazil in late 2020. In May of that year, United States bans most non-US citizens from traveling to the country from Brazil, this restriction remains in effect until November 2021. But Gamma was detected in the United States in January 2021 and soon spread to dozens of states.

Since Gamma never established worldwide dominance, examining its spread provided a “cleaner” picture of the effectiveness of travel bans. said Tetyana Vasylyeva, a molecular epidemiologist at the University of California San Diego and author of the study. “Let’s say when it comes to studying variables like Delta — something that causes a huge epidemic everywhere — sometimes it’s really hard to find patterns because it happens on such a large scale and so quickly,” he said. .

Dr. Fauver said there is an understandable urge to focus on the future in an ongoing global health emergency with a rapidly changing virus. And as the world’s attention turned to Delta and then Omicron, he and his colleagues debated whether to continue researching the old news Mu.

Dr. Fauver said, “’Does anyone care about Mu anymore?’ We were like,” he said. “However, we think there is still room for high-quality studies that ask questions about previous variants of anxiety and try to look back at what happened.”