How Concerned Should We Be About the
Mu Variant?

Damian McNamara

September 09, 2021

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Now that we're halfway through the Greek alphabet for naming SARS-CoV-2 variants, it is clear that some are more worrisome than others. Only four so far have raised enough alarm to warrant a World Health Organization 'variant of concern' designation — Alpha, Beta, Gamma, and Delta.

And now there's a new one to add to the list: Mu, now categorized as a WHO variant of interest.

Even though information and data on the Mu variant, officially known as lineage B.1.621, is scarce, we asked two experts in virology what it might have in store for us.

Medscape spoke with Jesse Erasmus, PhD, director of virology at HDT Bio and acting assistant professor at the University of Washington School of Medicine in Seattle, and Pedro Piedra, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas. The interview has been edited for length and clarity.

The Mu variant was first identified in Colombia, South America in January, so it's been around for 8 or 9 months. Any idea why is it getting more attention now?

Dr Pedro Piedra

Piedra: Like with any new variant, once you see it identified or spreading around parts of the country, it's something to take notice of. One is seeing Mu, not in any high numbers or high percentages, but we are detecting it in different places throughout the United States. That makes it of interest.

According to the CDC website that tracks the proportion of variants in the United States, Delta still almost completely predominates, whereas the Mu variant accounts for only about 0.1%. Any variant can become a variant of concern, but why do you think Mu is getting attention at the moment?

Erasmus: What is most likely driving the increased interest is the idea that we are looking at mutations associated with variants that we already know about, like Delta. It looks like Mu has mutations already in Delta but it also has mutations from Alpha or B.1.1.7, which was also known to be highly transmissible.

There's this idea that if you take a mutation from one variant and combine it with a mutation from another, you get a 'super mutant' virus that is going to wreak havoc. When in fact that is not necessarily the case.

I would say at this point — wisely so — it's a variant of interest.

On the other hand, Mu has been identified in over 40 countries and 49 states — every state except Nebraska. Does that say something about transmissibility?

Dr Jesse Erasmus

Erasmus: That would depend. You should talk to a genomic epidemiologist for a definitive answer. But these variants can arise via two different pathways: One is a single source of a new variant that gets transmitted globally and it can be traced to a single, emergent event. In my view that is very unlikely.

The other scenario is 'convergence evolution' when the variant emerges in multiple, separate instances. They perhaps provide some fitness to the virus. There can be multiple pathways through which a virus can arrive at this combination of mutations, which is probably more likely.

Also, if it does have an enhanced rate of transmission, we would expect to see a higher proportion of cases relative to the Delta variant.

Piedra: I would say at this time it's way too early. We really need to focus now on getting over this fourth wave of COVID, which is really Delta-driven. It will be important, as this slows down or this wave comes to an end, to see which variant will show up next.

Perhaps now that the population is more immune to that [Delta] virus, then another variant may come up. Our population is ever changing, with different proportions of people vaccinated in a city, state, or the country. Again, the population immunity changes over time. That immune pressure helps to select a variant for that particular area.

Is there any reliable information on Mu's potential for vaccine evasion?

Erasmus: Mu has the E484K and the K417N mutations identified in the Beta variants. The Beta variant is currently more immune-resistant than even the Delta variant. So it's definitely a valid hypothesis, and we're still waiting on more data to confirm.

A preprint study came out earlier this week and indeed demonstrates that Mu is slightly more vaccine resistant than the Beta variant.

When we talk about vaccine escape, we have to be very careful to specify this is escape from infection, not from serious disease. Even against the most vaccine-resistant variant out there, the vaccines still protect against disease.

Since Mu has mutations from both the Delta and Beta variants, is that a reason for concern?

Piedra: This raises the question of whether this variant is going to be more resistant to antibodies generated by the vaccine.

That was always a major concern for the Beta lineage. But for whatever reason, it did not seem to be as fit as the Delta variant in the US and worldwide. Delta replaced everything.

It goes to show you that, at a particular time and at a particular place, there is a variant that seems to be a better fit [that is able to become dominant] because it is the perfect variant at the perfect time.

The question is: Is the Mu variant going to be like that, and the answer is we don't know. So we need to keep track of it and look for the early signs of what will be the next wave when it comes.

Is the genomic sequencing of SARS-CoV-2 variants robust enough now in the US to accurately reflect the actual prevalence of each strain?

Erasmus: That's a really good question. There are definitely arguments that we could be doing a better job. There are certainly hot spots of very adequate genomic surveillance, like at Columbia, Yale, and here at the University of Washington. It is biased toward areas that have robust genomic sequencing workflows.

Piedra: I think one can always being doing better and we can always have more regional data. But we are doing much better than we were at the beginning.

A final but very important question: What is the right way to pronounce Mu?

Erasmus: (laughs) The way I pronounce it is m'yoo.

Piedra: M'yoo. It's the Greek letter Mu.

You can hear the pronunciation here.

Piedra has no relevant financial relationships to disclose. Erasmus is an employee and shareholder of HDT Bio, a company developing a COVID-19 vaccine.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter:  @MedReporter.

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