Oct. 6, 2021 -- Amid the Delta variant summer surge in COVID-19 cases, hospitalizations, and deaths, some experts warned that the next potential threat was starting to emerge: the Mu variant of the coronavirus.

Mu made headlines because its specific mutation meant it could evade vaccine immunity — spiking a new fear among the immunized.

But then an interesting thing happened — the prevalence of Mu in circulation in the U.S. dropped off quickly over a matter of weeks.

The robust transmissibility of the Delta variant allowed it to remain the dominant coronavirus strain, despite the risk from Mu, some experts believe.

"In a competition between Delta and Mu, even though Mu is likely more vaccine-resistant than Delta, the sheer transmission advantage could easily explain the disappearance of Mu," says Jesse Erasmus, PhD, director of virology at the pharmaceutical company HDT Bio, and acting assistant professor at the University of Washington School of Medicine in Seattle.

Still, we should not let our guard down, says Pedro Piedra, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston.

"In the United States we did not see the Mu variant taking off like Delta variant did, but that does not mean it might not," Piedra says.

Monitoring of Mu over time remains warranted, he says.

The Mu variant was first reported in the U.S. in March and April, although cases only numbered in the single digits. The 7-day rolling average of cases from the Mu variant increased to 1% of all U.S. cases on May 8, to 2% a few weeks later on May 29, and continued climbing to a peak of 3% on June 22, according to figures from Outbreak.info.

Then, the Mu cases began to drop at about the same rate during July, decreasing to 2% on July 9 and 1% on July 22, and less than 0.5% in August. The number of cases from Mu was back to single digits by September. The most recent was reported Sept. 20.

Still, the Mu variant was detected in 49 of 50 states in July (all except Nebraska, which was not reporting COVID-19 data at the time). Later, Mu was reported in all 50 states, the District of Columbia and Puerto Rico.

Yet, David Dowdy, MD, associate professor of epidemiology at Johns Hopkins Bloomberg School of Public Health in Baltimore, says Mu’s disappearance shouldn’t be a surprise.

"Mu never really had that much of an advantage over Delta to start with," Dowdy says.

"We, as a human race, always are on the lookout for these new variants — to see if anything might be bubbling up. As we do that, we are going to have some false starts.

"There are going to be some variants that look like they're more transmissible, just because they were in the right place at the right time," he says.. "The only way to find out if that is the case is to follow it over time."

Mu Has Multiple Mutations

Robert Shafer, MD, believes the initial concerns about Mu were warranted. Mu has mutations that help it reproduce and others that raise its potential for beating our immune systems.

Mu has at least three mutations observed in other viruses or previous coronavirus strains that help it reproduce, Shafer says.

"Mu also contains multiple mutations that enable it to evade … immunity," said Shafer, professor of medicine in the Division of Infectious Diseases at Stanford University in California.

Though these mutations may be just numbers and letters to many people, they're important to those trying to anticipate the virus' next move.

"Based on the large number of escape mutations, it is extremely reasonable to expect that this variant might pose a threat to populations with increasing numbers of persons who have become vaccinated and/or previously infected," Shafer said. "However, despite its initial spread and slight increase in multiple countries, it has not made inroads into the dominance of the Delta variant, except possibly in Colombia where it originated."

To understand this, it is important to recognize that spike mutations only partially explain the success of a coronavirus variant. Mutations outside of the spike may be even more important in understanding transmissibility.

Mu Being Monitored

Although the World Health Organization continues to classify Mu as a 'variant of interest' globally, the CDC lists Mu simply as a 'variant being monitored.'

The CDC counts 10 variants in the variant being monitored group, including three once considered variants of concern: the Alpha, Beta, and Gamma strains.

The CDC only considers Delta a variant of concern.

There is a fourth category in the U.S. — 'variant of high consequence' — and so far, no coronavirus strain has reached this threat level. A variant could qualify if tests fail to detect it; if evidence shows a significant reduction in vaccine effectiveness; if a high number of infections occur among vaccinated individuals; and if more severe disease and increased hospitalizations occur, according to the CDC.

Will We Hear More About Mu?

Predicting the future of viral strains during a pandemic can be tricky. But when asked, Erasmus was willing to make some predictions.

"I think many variants will remain 'of interest' until they are either definitively extinct or become upgraded to a variant of concern," he says.

Furthermore, increasing the country’s immunity to the Delta variant through natural infection or vaccination could lead to one of two scenarios. One possibility is that as Delta cases go down, another variant could take its place, Erasmus said.

It is unlikely to be Mu, however.

"In the end, I think it will mostly be variants with enhanced transmission capability that will ultimately be responsible for subsequent waves," Erasmus says.

A second, more positive scenario is that the increase in immunity against the Delta variant will lead to fewer COVID-19 cases overall. The drop in new infections would mean fewer opportunities for Mu or another variant to gain traction in the population over time.