UK PHE: E484K Mutation Detected In A Small Number of B.1.1.7 Variant VIruses

 

#15,779

While its true significance isn't yet known, yesterday the UK's PHE (Public Health England) announced the detection of the E484K mutation in a handful (n=11) of B.1.1.7 (aka VOC 202012/1) variant viruses in a very brief passage (see above) from their 5th Technical Briefing Report on the UK Variant. 

While the reported number is small, it should be pointed out only a small fraction of UK COVID tests undergo full genomic sequencing, and those results are generally delayed by two weeks.

Most B.1.1.7 variants are presumptively identified in the UK by the proxy S gene target failure (SGTF) which is picked up by the ThermoFisher TaqPath assay. Meaning that the actual number of E484K bearing variants in the UK - while likely still small - could be higher. 

B.1.1.7 has already been linked to a 25%-40% increased attack rate, and while the results are preliminary, may be linked to a slightly higher mortality rate (see BMJ: New UK Variant May be Linked to Increased Death Rate, Early Data Indicate) as well.

While all of this makes B.1.1.7 a formidable foe, its one saving grace has been its susceptibility to the current crop of vaccines. 

The presence of the E484K mutation - which has turned up independently in several different variants in both Brazil and South Africa - potentially complicates this picture, although how much of an impact it might have on the B.1.1.7 variant is unknown. 

E484K has been linked to reduced antibody recognition, which is feared might increase reinfection risks and potentially lower the effectiveness of current vaccines, monoclonal antibodies, or convalescent plasma (see PrePrint: SARS-CoV-2 501Y.V2 Escapes Neutralization by South African COVID-19 Donor Plasma).

A great deal would depend upon how prevalent this mutation becomes in the B.1.1.7 variant.  If it remains a minor player, then its impact on public health - regardless of 484K's impact on COVID antibody recognition - would be small. 

The concern is this E484K mutation has shown up repeatedly, and independently, in COVID variants emerging form several parts of the world, suggesting this is a likely product of `convergent evolution'. Meaning it could show up with increasing frequency in the months ahead. 

Amino acid substitutions are considered random, and most convey no special advantage to the virus. Many are neutral or even detrimental, and those viruses tend to fade away. 

There are only a limited number of mutations (or combinations of mutations) that deliver a genuine fitness boost - and while they may only show up by chance - when they do, they tend to help the virus to survive and thrive. 

E484K appears to be one of those mutations (alone or in concert with other mutations), as it has been linked to aiding with escape from neutralizing antibodies. A recent study on the BioRxiv preprint depository delves into the role played by E484K in the evolution of SARS-CoV-2 in 3 Brazilian variants.

E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil

Patrícia Aline Gröhs Ferrareze, Vinícius Bonetti Franceschi, Amanda de Menezes Mayer, Gabriel Dickin Caldana, Ricardo Ariel Zimerman, Claudia Elizabeth Thompson

doi: https://doi.org/10.1101/2021.01.27.426895

This article is a preprint and has not been certified by peer review [what does this mean?].

 

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Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people since its beginning in 2019. The propagation of new lineages and the discovery of key mechanisms adopted by the virus to overlap the immune system are central topics for the entire public health policies, research and disease management. 

Since the second semester 2020, the mutation E484K has been progressively found in the Brazilian territory, composing different lineages over time. It brought multiple concerns related to the risk of reinfection and the effectiveness of new preventive and treatment strategies due to the possibility of escaping from neutralizing antibodies. To better characterize the current scenario we performed genomic and phylogenetic analyses of the E484K mutated genomes sequenced from Brazilian samples in 2020. 

From October, 2020, 43.9% of the sequenced genomes present the E484K mutation, which was identified in three different lineages (P1, P2 and B.1.1.33) in four Brazilian regions. We also evaluated the presence of E484K associated mutations and identified selective pressures acting on the spike protein, leading us to some insights about adaptive and purifying selection driving the virus evolution.

(Continue . . . )

Even if the E484K mutation in COVID variant B.1.1.7 turns out to be a flash in the pan, this variant is expected to become the dominant COVID virus in the United States (see MMWR: Emergence Of SARS-CoV-2 B.1.1.7 Lineage — United States, Dec 29, 2020–Jan 12, 2021) and across much of the world in the months ahead. 

If E484K becomes fixed in B1.1.7 - or starts turning up in other easily spread variants -  that could potentially complicate matters even further. 

While no one would argue that this latest discovery is good news, we don't have enough data (yet) to say how big of an impact - if any - this B.1.1.7 (E484K) variant will have. 

Stay tuned.