Over the course of the pandemic, several "lesser lineages" of the coronavirus have driven regional surges "but never swept to global dominance." Writing for the New York Times, Emily Anthes highlights some of the lessons we can learn from these "vanishing variants."

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A 'vanishing variant'

In 2021, the mu variant was spreading across Colombia and had been detected in dozens of other countries. As a result, the World Health Organization (WHO) designated it a "variant of interest."

"Mu was starting to make some noise globally," said Joseph Fauver, a genomic epidemiologist at the University of Nebraska Medical Center and an author of a recent study on the variant.

"It contained a couple of mutations that people had been watching very closely," said Mary Petrone, a genomic epidemiologist at the University of Sydney and an author of a new paper on mu. The variant's spike protein contained several mutations documented in other immune-evasive variants, including beta and gamma.

In their analysis of genomic sequences of mu samples from around the world, researchers were able to reconstruct the variant's spread.

Overall, genomic surveillance in many areas of South America was "patchy and incomplete," saidJesse Bloom, an expert in viral evolution at the Fred Hutchinson Cancer Research Center. "If there had been better surveillance in those regions, possibly it would have been easier to make a faster assessment of how worried to be about Mu."

In addition, the variant contained a rare frameshift mutation that was flagged as an error when scientists tried to upload the genomic sequences to GISAID—an international database of viral genomes that is used to track new variants—resulting in significant delays in publicly sharing mu sequences.

"The genome itself was basically creating artificial surveillance gaps," Fauver said. "It resulted, at least in our experience, in us not getting data out for weeks when normally we're trying to get it out in days."

With the surveillance gaps and the variant's immune evasiveness, mu seemed to be "poised to take off." However, that is not what happened. Instead, "it fizzled," Anthes writes. "Today, the variant has all but vanished."

Studying previous variants can help health experts prepare for future surges

While it is critical that public health experts understand widespread variants, like omicron, many experts believe there are important lessons to be learned from the other "lesser lineages."

"This virus has no incentive to stop adapting and evolving," said Joel Wertheim, a molecular epidemiologist at the University of California, San Diego. "And seeing how it did that in the past will help us prepare for what it might do in the future."

According to Anthes, "[s]tudying successful variants tells only half the story."

"Variants that do not become dominant are, in a way, negative controls," Petrone said. "They tell us what didn't work, and, in doing so, help to fill in knowledge gaps around variant fitness."

Studying previous variants can also provide insight into which measures were most effective in containing the virus.For instance, a new study of the gamma variant provides further evidence that the international travel bans imposed in the United States are unlikely to prevent the global spread of a future variant.

Since the gamma variant never triggered a worldwide surge, studying its spread painted a "cleaner" picture of the effectiveness of travel bans, according to Tetyana Vasylyeva, a molecular epidemiologist at the University of California, San Diego. "When it comes to studying variants like, let's say, Delta — something that has caused a major outbreak in every place — it is really difficult at times to find patterns, because it happens on a very large scale and very fast," Vasylyeva said.

"We can't view a new variant in a vacuum, because it comes about in the shadow of all of the variants that came before it," said Wertheim, who was an author of the study.

"Indeed, the clash of variants past reveals that success is highly dependent on context," Anthes writes. For instance, New York City is believed to have been the birthplace of the iota variant, which was first detected in virus samples collected in November 2020. "And so it got a foothold early on," said Petrone. Notably, the iota variant remained the dominant variant in the city even after the highly transmissible alpha variant arrived, but it eventually faded away.

In comparison, in Connecticut—where both iota and alpha were detected in January 2021—the variants progressed differently. "Alpha just kind of took off immediately, and Iota didn't stand a chance," said Petrone, who led a study of the variants in both regions.

During an ongoing global health emergency, with a fast-changing virus, there is an understandable impulse to primarily focus on future variants, Fauver said. However, as the world's attention turned to delta and then omicron, Fauver and his colleagues discussed whether to continue their study of the "lesser" mu variant.

"We were like, 'Does anyone care about Mu anymore?'" Fauver recalled. "But we think there's still room for high-quality studies that ask questions about previous variants of concern and try to look back on what happened." (Anthes, New York Times, 5/4)