India Finds 'Double Mutant' COVID Variant. How Worried Should Americans Be?

Reports of a "double mutant" virus have emerged after India's Ministry of Health announced that COVID samples had been found with two mutations.

The two mutations—E484Q and L452R—could cause increased transmission and resistance to vaccines and have been found in about 15 to 20 percent of samples from the Maharashtra region, the health ministry said.

The findings were reported by India's INSACOG laboratory group, which has been mapping the genetic code of virus samples from across the country.

However, information uploaded on Thursday to GISAID—an international initiative to share virus gene sequencing data—showed that many viruses found in India with the L452R and E484Q mutations actually have six mutations in total, not two.

Virus samples showing up with multiple mutations is not uncommon, and two mutations is not a lot, according to Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport.

Kamil told Newsweek: "The term 'double mutants' leaves much to be desired, not least of all because it is inaccurate. In a quick skim of GISAID data, these mutants always, or almost always, have more than just two spike mutations. Spike mutations are only one type of many different mutations across the viral genome."

He added on Twitter: "Probably best not to call them 'double mutant' as the news reports have... but maybe sexta-mutants."

As well as E484Q and L452R, spike mutations found in the samples include P681R, E154K and D614G, according to the data.

Kamil said the E484Q mutation was similar to the E484K mutation found in the U.K.'s Bristol variant, as well as the Brazil and South Africa variants, which is known to give the virus a resistance to the body's immune response and make the virus better at reinfecting people, potentially disrupting vaccine efficacy.

He told Newsweek: "L452R is not as well studied in vitro as E484K/E484Q. It may have a small effect on transmissibility.

"I am not able to comment on whether this is a particular concern. I'm sure some scientists might say it is, but 'variants' are common at this point and I'm not convinced that there's a special disease risk, though I would agree the E484Q mutation provides a mechanism that could penetrate herd immunity, and the P681R mutation might enhance transmissibility—but that would need to be tested.

"So far, there are not a huge number of these viruses in GISAID, only 63 that have P681R+E484Q+L452R. But the lineage is very new, first seen in Singapore from a sample with a Feb 26 collection date. Since then already in the UK, Germany, Canada, India, Australia, and New Zealand … I'm pretty sure it is all one lineage."

Vineet Menachery, a virologist at the University of Texas Medical Branch, said: "It is hard to comment on the new variant without having functional data. The E484Q mutation is potentially concerning, similar to E484K as it disrupts a potential antibody binding site. We know several monoclonal antibodies target this site, rendering these treatments ineffective against E484K; I'd anticipate the same with E484Q.

"The L452R mutation is also of concern given its relationship to [the] California variant and association with antibody escape mutant predictions. It is also in the receptor binding domain, but it is not clear if it helps binding or not. Obviously, the combination of both does suggest a concern, but it is hard to determine based solely on data from sequencing."

Arinjay Banerjee, a virologist and postdoctoral researcher at McMaster University in Canada, said: "Multiple mutations within the spike protein and across the entire genome of the virus are common as coronaviruses evolve. This has also been observed for SARS-CoV-2.

"There is no need to panic, but we should certainly study these mutations and combinations of mutations."

This article has been updated to add extra notes and clarification from Jeremy Kamil.

Correction 03/29/2021, 11:25am ET: This article has been updated to correct the spelling of "L452R." It has also been updated to clarify the Bristol variant found in the U.K., rather than the U.K. variant, carries the E484K mutation.

Scientist holding a COVID sample
A laboratory technician displays a coronavirus testing tube in New Delhi on April 7, 2020. Teams from India's INSACOG virus sampling team uploaded data on the mutations to the GISAID data network on Thursday. Sajjad Hussain/AFP/Getty