'Double mutant' COVID variant emerges in the U.S. Here's what that means

Variant has two notable mutations in key region
Double mutant
Posted at 6:02 PM, Mar 31, 2021
and last updated 2021-03-31 21:52:56-04

SAN DIEGO (KGTV) -- Scientists are investigating a coronavirus variant in India they’ve dubbed a “double mutant” whose emergence coincided with a rapid spike in cases.

Using a database of viral sequences, ABC 10News found 13 cases of the double mutant in the U.S., including 10 cases in California. The first U.S. case was detected in a sample collected in Los Angeles on January 8.

But what exactly is a double mutant? How did it form? And ultimately, what impact will it have?

What is a double mutant?

The name “double mutant” is misleading, says UC San Diego virologist Dr. Davey Smith.

All of the variants you’ve heard of -- U.K., South Africa, Brazil -- carry multiple mutations (between 5 and 11 mutations in their spike proteins alone).

In this case, the phrase “double mutant” has nothing to do with the total number of mutations the variant carries. Instead, Indian health officials gave the variant this nickname because it carries two important mutations in a critical part of the virus: the part of the virus that attaches to cells, officially called the “receptor-binding domain.”

That part of the virus is also the best target for antibodies. When antibodies block the receptor-binding domain, the viral particle is incapacitated.

“Why that's concerning is that as we all get vaccinated and we start developing antibodies, perhaps these mutations make it more likely for us to get infected even after a vaccine,” Dr. Smith said. “None of that’s really borne out in real life, so to speak, but scientists are looking at it.”

These two important mutations are called L452R and E484Q. The letters and numbers are scientific shorthand to express changes in the viral code. E484Q means at the 484th position in the sequence, an E (glutamic acid) was replaced by a Q (glutamine).

Both the Brazil and South Africa variants have a similar mutation at the 484th position (E484K) that has been shown in lab tests to make the virus more elusive to the immune response.

The flagship mutations in the “double mutant” had appeared in samples before, but only separately. Cases in India’s state of Maharashtra were the first instances where they were found in tandem.

How did it form?

The one-two punch in the double mutant represents traits that were previously found in separate variants. E484Q was circulating in samples in India, but L452 was first detected in the California variant.

It’s not uncommon for variants to pick up mutations that were found elsewhere, Smith said.

Recently, scientists in the UK noticed that some sequences of B.1.1.7 now contain E484K, the escape mutation once confined to the Brazil and South Africa variants. (That new combo variant is called the Bristol variant.)

This can happen two ways, Smith said. When a virus replicates inside a person, it often makes mistakes while copying itself. When the virus hopscotches from person to person, advantageous mistakes get passed on.

In one scenario, a person might have been infected with a virus carrying an E484Q mutation, but when their cells started making virus children, they produced ones that also contained L452R.

Another possibility is that one person might have been infected by two different variants at roughly the same time (imagine a person wedged between two sick people on a subway, each carrying a different variant).

Inside that unlucky fellow’s cells, the virus might replicate using bits of both variants.

“Some viruses can ‘recombine’ and that means taking a little bit of genetic material from one of the variants, and then genetic material from another one of the variants, to make a new offspring,” Dr. Smith said.

What impact will the double mutant have?

Scientists still need to learn a lot more about the double mutant before deciding if it’s worth classifying as a “variant of concern,” like the ones first detected in the UK, South Africa and Brazil.

But there’s plenty of data warranting further study. India is in the midst of a rapid surge in cases, and on Wednesday, the country reported its highest daily death toll of 2021. One state, Maharashtra, is responsible for the bulk of the cases. Maharashtra is reporting 10 times as many cases as any other state.

Last week, Indian health officials announced the double mutant was present in 15 to 20 percent of the sequenced cases from that state.

But health officials say there’s no conclusive evidence yet the double mutant is responsible for the surge., a tool built by Scripps Research using the database GISAID, shows 13 cases of variants carrying both the L452R and E484Q mutations in the United States. The most recent instance was from a sample collected March 6, suggesting the double mutant is not yet a significant source of spread.