Denmark: SSI Risk Assessment On E484K SARS-CoV-2 Mutation

 

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Although researchers are striving to decipher the impacts and risks of all of the recurring mutations in the SARS-CoV-2 genome, one in particular - E484K - has garnered a great deal of attention over the past few months. 

• First, because it continues to pop up independently in emerging variants around the globe (B.1.351 in South Africa, P1, P2 and B.1.1.33 in Brazil, and in a new variant of B.1.1.7 in the UK, among others). 

• And second, because it has been linked to reduced antibody recognition, which 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).
  

While a single mutation in a genome the size of the SARS-COV-2 is rarely enough to change the behavior or impact of the virus, it is located in the crucial receptor-binding domain of the spike protein, and it appears to work in concert with a number of other common mutations to enhance the fitness of the virus. 

Its recent acquisition by a small number of B.1.1.7 variants in the UK (see UK: NERVTAG Names New COVID VOC (Variant of Concern)) - a variant already known for its increased transmissibility -  has raised concerns over the continual evolution of the virus outside of the UK. 

Yesterday Denmark's SSI (Statens Serum Institute) published the following update, and a technical note, on the detection of the E484K mutation in their nation.  

The good news is that the E484K mutation in the B.1.1.7 variant has not been detected, although 67 other instances have been identified.  Of those, only 8 are linked to the B.1.351 (South African) variant, indicating this mutation continues to appear in other variants around the globe. 

First the (translated) summary, followed by (translated) excerpts from the technical note.  

Status of the covid-19 virus mutation E484K

Until 12 February, 67 cases of the E484K mutation have been found in Denmark. It shows a new note from the Statens Serum Institut.

Last edited 13 February 2021 

The Statens Serum Institut (SSI) has prepared a status and a risk assessment for how many cases of covid-19 have been detected in Denmark with the E484 mutation.

According to the new note from SSI, as of February 12, 67 cases of the E484K mutation have been detected. The 8 of them are cases where people were infected with the covid-19 variant B.1.351, which also contains the E484K mutation.

So far, the E484K mutation has not been found among samples with the covid-19 variant B.1.1.7.

What is the E484K Mutation?

The E484K mutation is a mutation in the spike protein to which antibodies from the vaccines bind. In laboratory experiments, studies have shown that antibodies from vaccines do not work as well on viruses with the mutation. The mutation has been found in several covid-19 variants including B.1.351 and P.1.

When you keep an eye on it, it's because studies have shown that it gives reduced sensitivity to antibodies. However, this does not mean that the vaccines are not expected to work, nor is there any evidence that the mutation itself causes an increased infectivity.

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Excerpts from the (translated) risk assessment follow. You will note that the SSI finds local transmission of the E484K mutations in variants other than the `usual suspects' of B.1.351 and P.1. 

February 12, 2021

Epidemiological risk assessment for E484K

The Statens Serum Institut (SSI) has been asked for a status and risk assessment on cases with covid-19 infection where the E484K mutation has been detected. A status of number is required, travel relationship and whether it is considered to be a societal infection with virus variants, where The E484K mutation is detected as well as an assessment of infectivity and severity. 

The Danish Agency for Patient Safety and the Danish Medicines Agency have contributed to the preparation of the risk assessment.

Background

The E484K mutation is a substitution of Glutamate (E) at position 484 in the prescription binding domain on the nail protein. This mutation is found in several of the new variants of interest as B.1.351 and P.1, which are designated as Variants of Concern (VOC)

The mutation is called an escape mutation, as studies have shown that E484K results in decreased sensitivity to antibodies. There is no evidence that the mutation in itself causes an increase infectiousness. But the E484K appears to have originated independently and has been shown to occur at several different variants of SARS-CoV-2., including B.1.1351 or P.1, all of which have the mutation in combination with the N501Y mutation, which increases infectivity.

In England have some examples of the E484K mutation were also found among the B.1.1.7 variant. There is not currently detected the E484K mutation among samples with the B.1.1.7 variant in Denmark.

Status of the occurrence of the variants in Denmark

A total of 67 cases of the E484K mutation have been detected in Denmark, including 8 cases. where B.1.351 has been detected, which also contains the mutation. This means that per 12. February 2021, 59 cases of the E484K mutation have been detected, where B.1.351 is not involved or P.1.

The Danish Agency for Patient Safety (STPS) has informed SSI that 10 of the cases are related to travel activity in Nigeria, Brazil and Switzerland. 10 people associated with outbreaks at school in The capital, and 9 people associated with the workplace in Odense.

The Danish Agency for Patient Safety has been continuously informed of all cases of the E484K mutation, and intensified contact tracking has been initiated in line with

contact tracing for handling VOC. 

(SNIP)

Epidemiological risk assessment: 

Concerns have been raised about the presence of virus variants with the E484K mutation due to several studies showing evidence of decreased efficacy of antibodies both from previous infections and from  certain vaccines on virus variants with the mutation.

Currently, the E484K mutation is part of 2 of the VOC (B.1.351 and P.1), which are considered to pose a threat, as the mutation occurs together with the N501Y mutation, which is considered to increased infectivity, and thereby a significant spread advantage. Cases have been reported with B.1.1.7 where E484K has also been found in the UK.

There is international concern about the presence of the E484K mutation, and SSI shares this concern. At present, it is not clear what significance the mutation has when it does not detected in combination with N501Y, as in B.1.351 or P.1, and more knowledge is needed about the mutation. 

SSI therefore closely monitors the occurrence of the mutation and is in the period from December 29, 2020 until February 5, a total of 59 cases with the mutation were detected (excl. 8 case of B.1.351). The 484K mutation has been detected in samples from cases in 4 out of 5 regions, and the proportion related to travel activity is around 17%.

Information from the Danish Agency for Patient safety suggests that there is a local spread of infection with the mutation.

Based on a precautionary principle, cases of detected E484K mutation are handled in line with other VOCs (B.1.1.7, B.1.351 and P.1.) in order to contain transmission with the mutation. This includes rapid orientation of STPS upon discovery of the mutations as well intensified contact tracking in STPS ’Task force.

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