Vanishing Variables: Lessons from Gamma, Iota, and Mu

In early 2021, scientists in Colombia discovered a worrying new type of coronavirus. This variant, eventually known as Mu, had several worrying mutations that experts believe could help it evade the immune system’s defenses.

During the following months, Mo spread rapidly in Colombia, Fueling a new surge in Covid-19 cases. By the end of August, it was discovered in dozens of countries, and the World Health Organization has appointed her “Variable of interest”.

Joseph Fofer, a genetic epidemiologist at the University of Nebraska Medical Center and author of A recent study on the variable.

Then it vanished. Today, the variant has completely disappeared.

For every delta or omicron, there are gamma, iota, or mu variables, variables that led to local outbursts but never swept global dominance. And while understanding Omicron remains a critical public health priority, there are lessons to be learned from these fewer strains, experts say.

“This virus has no incentive to stop adaptation and evolution,” said Joel Werthem, a molecular epidemiologist at the University of California San Diego. “And knowing how you did it in the past will help us prepare for what you might do in the future.”

Studies of surveillance also highlight surveillance loopholes and policy errors — providing more evidence that the international travel ban in America has not been effective — and on what makes the virus work, suggesting that in the early stage of the pandemic, transmissibility was More important than immune evasion.

The research also highlights how important context is; Variables that have an impact in some places do not get a foothold in others. As a result, it is difficult to predict which variables will rise to dominance, and staying on top of future variables and pathogens will require comprehensive monitoring in near real time.

“We can gain a lot by looking at the viral genome sequence and saying, ‘One is probably worse than the other,'” Dr Werthem said. .”

Here Mu . is seen

The coronavirus is constantly changing, and most new variants go unnoticed or named. But others are sounding the alarm, either because they are quickly becoming more common or because their genomes look ominous.

Both were true for Mo as he spread to Columbia. “It contained a couple of mutations that people were watching closely,” said Marie Petron, a genetic epidemiologist at the University of Sydney and author of Moe’s new paper. Several spike protein mutations have been documented in other immunologic variants, including beta and gamma.

In the new study, which has not yet been published in a scientific journal, scientists compared the biological properties of Mu with those of Alpha, Beta, Delta, Gamma and the original virus. They found that Mu did not replicate faster than any other variant, but it was the most immune-elusive—more resistant to antibodies than any known variant besides Omicron.

By analyzing the genomic sequences of Mu samples collected from around the world, the researchers reconstructed the prevalence of the variant. They concluded that Mu most likely appeared in South America in the middle of 2020. It was then circulated for several months before it was discovered.

He said genomic surveillance in many parts of South America was “incomplete and incomplete” Jesse Bloom, an expert in viral evolution at the Fred Hutchinson Cancer Research Center in Seattle. “If there had been better monitoring in those areas, perhaps it would have been easier to quickly assess how concerned Mo is concerned.”

Mo presented another challenge as well. She happened to have a type of mutation, known as a frameshift mutation, which was rare in coronavirus samples. These mutations were flagged as errors when scientists, including Dr. Fofer, attempted to upload their Mu sequences to GISAIDan international repository of viral genomes used to monitor novel variants.

This complication has caused a delay in the public participation of Mo sequences. The researchers found that the time between when a virus sample was collected from a patient and made public on GISAID was always longer for Mu cases than for Delta cases.

“The genome itself was essentially creating artificial gaps in surveillance,” Dr. Faufer said. “This has resulted, at least in our experience, in that we don’t have the data for weeks when we normally try to publish it within days.”

(The researchers stressed the importance of GISAID’s quality control systems, and the repository has fixed the problem.)

Combine these monitoring gaps with Mu’s immune evasions, and it looked like the alternative was about to take off. But that is not what happened. Instead, scientists found that Mo spread from South and Central America to other continents but did not spread widely once it got there. “This was an indication that this variant was not necessarily as appropriate in perhaps North American and European populations as we would expect,” Dr. Petron said.

That was most likely because Mu found himself competing with an even more awesome variant: delta. Delta was not as skilled at evading antibodies as Mu, but it was more transmissible. “So, eventually, Delta spread more widely,” Dr. Bloom said.

Right choice, right time

Studying successful variants only tells half the story. “Variables that do not become dominant are, in a way, negative controls,” said Dr. Petron. “They tell us what didn’t work and, in doing so, help fill knowledge gaps about variable fitness.”

Delta outperformed several immunogenic variants besides Mu, including Beta, Gamma and Lambda. This pattern suggests that immune evasion alone wasn’t enough to allow the variant to outgrow a highly infectious version of the virus—or at least it wasn’t during the early phase of the epidemic, when few people had immunity.

But vaccinations and multiple waves of infection have changed the immune landscape. The scientists said the highly immune-elusive alternative should now have more of an advantage, which is likely part of the reason for Omicron’s success.

Another recent study suggested that the immune evading gamma in New York City Tend to do better In neighborhoods with higher levels of pre-existing immunity, in some cases because they were hit hard in the first wave of Covid. “We can’t see a new variable in a vacuum, because it comes in the shadow of all the variables that came before it,” said Dr. Werthem, who was an author of the study.

Indeed, the clash of variables in the past reveals that success depends largely on context. For example, New York City may have been the birthplace of the Iota variant, which It was discovered for the first time In virus samples collected in November 2020. “So he got an early foothold,” said Dr. Petron. Even after the arrival of the more portable Alpha variant, Iota remained the dominant variant in town for several months, before eventually fading out.

But in Connecticut, where Iota and Alpha debuted in January 2021, things went differently. “Alpha took off immediately, IOTA had no chance,” said Dr. Petroni, who led the operation. Study the variables in the two regions.

A similar pattern is already beginning to emerge with the multiple Omicron strains. In the United States, BA.2.12.1, a variant first identified in New York, took offWhile in South Africa, BA.4 and BA.5 are driving a new boom.

This is another reason to study the variants that have diminished, said Sarah Otto, an evolutionary biologist at the University of British Columbia. An alternative that was not well-matched to a particular time and place could take off elsewhere. In fact, it was probably Mo’s misfortune that he showed up so early. “Maybe there weren’t enough people with immunity to give a boost to this variant,” Dr. Otto said.

But the next worrisome variant could be a descendant, or something similar, of an immune-evading strain that never took hold, she said.

Looking at previous variables can provide insight into what worked – or didn’t work – to contain them. The new Gamma study provides further evidence of this International travel banat least as implemented by the United States, is unlikely to prevent the global spread of the variant.

Gamma was first recognized in Brazil in late 2020. In May of that year, The United States has banned most non-US citizens from traveling into the country from Brazil, a restriction that remains in place Until November 2021. However, gamma was discovered in the United States in January 2021 and soon spread to dozens of countries.

Since Gamma has never really dominated worldwide, its prevalence study provides a “cleaner” picture of the travel ban’s effectiveness, said Titiana Vasilyeva, a molecular epidemiologist at the University of California San Diego and an author of the study. “When it comes to studying variables like delta – something that’s causing massive outbreaks everywhere – it’s sometimes really hard to find patterns, because it happens on a very large scale and very fast,” she said.

Dr Faufer said that in the ongoing global health emergency, with a rapidly changing virus, there is an understandable reason to focus on the future. As the world’s attention turned to Delta and then Omicron, he and his colleagues debated whether to continue their study of the old news Mu.

Dr. remembers. “But we think there is still room for high-quality studies that ask questions about pre-existing variables of concern and try to reconsider what happened.”