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Inicio Enfermedades Infecciosas y Microbiología Clínica (English Edition) De novo emergence of the mutation E484K in a SARS-CoV-2 B.1.1.7 lineage variant
Información de la revista
Vol. 40. Núm. 9.
Páginas 520-522 (noviembre 2022)
Vol. 40. Núm. 9.
Páginas 520-522 (noviembre 2022)
Scientific letter
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De novo emergence of the mutation E484K in a SARS-CoV-2 B.1.1.7 lineage variant
Aparición de novo de la mutación E484K en una variante del linaje B.1.1.7 de SARS-CoV-2
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Mikel Urrutikoetxea-Gutierreza,c,
Autor para correspondencia
mikel.j.urruti@gmail.com

Corresponding author.
, Estibaliz Ugalde Zarragaa,c, Mikel Gallego Rodrigob,c, Jose Luis Díaz de Tuesta del Arcoa,c
a Hospital Universitario Basurto, Servicio de Microbiología Clínica, Bizkaia, Spain
b Hospital Universitario Cruces, Servicio de Microbiología Clínica, Bizkaia, Spain
c Grupo de Microbiología y Control Infección, Instituto Biocruces Bizkaia, Bizkaia, Spain
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Since its first description in December 20201, the SARS-CoV-2 variant of concern VOC-202112/01 (also known as lineage B.1.1.7, 20I/501Y.V1 or, recently, according to the WHO, simply alpha2) has been spreading all over the world. In our geographical area, it became predominant from the beginning of March 2021, accounting for more than 90% of new infections in June 20213. This is mainly due to the mutations that this variant accumulates in the gene that encodes the spike (S gene), especially in the receptor-binding domain (RBD). These mutations, especially the N501Y mutation that it shares with the beta (B.1.351 or 20H/501Y.V2) and gamma (P.1 20J/501Y.V3) variants of concern, among others, are related to an increased binding affinity of the spike with angiotensin-converting enzyme II and an increase in transmissibility4. These last two variants also share the E484K mutation, also in the RBD, which could be related to a certain degree of escape from the action of the vaccines5. Therefore, when the first sequences of the B.1.1.7 lineage with the E484K mutation emerged, the British authorities declared them variants of concern VOC-202102/026. However, the cluster in which these variants were framed does not seem to have been as successful and represents only 0.225% of the sequences of the B.1.1.7 lineage included in the GISAID (Global Initiative on Sharing All Influenza Data).

In accordance with our centre’s variant screening protocol, all SARS-CoV-2 positive samples with Ct <32 are tested using the Allplex™ SARS-CoV-2 Variants I Assay kit (Seegene, Korea), which simultaneously detects H69/V70, E484K and N501Y mutations. At the end of April, we identified a sample which was positive for all three targets studied. In addition to the sample from the patient who had all three mutations, samples from the other three positive cases from the family cluster of which the patient had been a close contact were sequenced, presenting a profile compatible with the B.1.1.7 lineage but without the E484K mutation. For the sequencing of the viral genome, the Ion AmpliSeq SARS-CoV-2 Research Panel (Thermo Fisher Scientific, USA) was used7. Libraries were prepared following the manufacturer’s instructions and loaded onto a 540 chip and the Ion GeneStudio™ S5 (Thermo Fisher Scientific, USA) platform. The genome was assembled using the IRMA plugin8 and its consistency was checked using the Integrative Genomics Viewer (IGV) program9. The Nextstrain webApp10 was also used for both clade assignment and visualisation of mutations. The sequences obtained by next-generation sequencing confirmed the results of the PCR variant screening techniques. The test sample presented the G23012A mutation that conditions the amino acid change in the E484K S gene. None of the other three samples had that mutation in the assembly, and the A readings at position 23012 accounted for less than 1% of the readings in each of the samples. Except for the G23012A mutation, the four strains of the family cluster were identical and had both the characteristic mutations of the B.1.1.7 lineage and some of their own (see Table 1).

Table 1.

Coverage of the mutations present in the family cluster.

  Test sample  Relative 1  Relative 2  Relative 3 
C241T  2935  7356  4892  3110 
C913T  5499  10533  7634  5110 
C3037T  6899  10817  8752  8597 
C3267T  1870  6997  4489  3645 
C4464T  7318  13962  8950  5797 
A5041G  3407  6980  4543  2567 
C5388A  4309  8448  5309  3474 
G5763A  7673  12951  9983  10079 
C5986T  2074  3458  1213  449 
T6954C  2822  7202  3136  933 
11288-11297  6911  11107  8345  7157 
C11668T  5339  7078  3973  2795 
C12439T  6903  11349  7622  6920 
C14407T  4004  6209  3489  2521 
C14408T  4006  6230  3496  2525 
C14676T  5486  8911  6115  4265 
T15096C  3185  5267  3462  3199 
C15279T  1811  6655  4096  2838 
T16176C  6050  11721  8117  9837 
C18647T  2354  6501  4085  3055 
21766-21772  5587  6261  5807  5072 
21994-21997  7153  7985  6569  5075 
G23012A  8771       
A23063T  2137  5422  4300  1691 
C23271A  4375  7485  6071  5999 
A23403G  13281  16004  13387  13398 
C23604A  9736  12985  11754  14791 
C23709T  7735  11037  9594  7600 
T24506G  14234  17157  15581  13242 
G24914C  9398  14695  11772  7804 
C27972T  25717  28812  39283  27683 
G28048T  25829  28835  39267  27589 
A28095T  12218  16000  19763  6728 
A28111G  12192  15990  19727  6687 
28274  9517  11135  18433  8315 
G28280C  10624  12112  19790  8916 
A28281T  10686  12175  19865  8933 
T28282A  10689  12181  19875  8936 
C28320T  10853  12294  20071  9036 
G28881A  6831  10521  12661  5721 
8882A  6840  10531  12673  5728 
G28883C  6841  10531  12673  5728 
C28977T  6715  10284  12336  5378 

Despite belonging to the B.1.1.7 lineage and also exhibiting the E484K mutation, the sequence of our sample did not share the rest of the characteristic mutations of VOC-202102/02. The appearance of this mutation was therefore probably independent to those found in February 2021 in the United Kingdom, similar to other synchronous appearances of this mutation. In this case, the epidemiological chain of transmission is quite clear, since the infection of the patient with the E484K mutation appeared later: one week after the rest, and when the patient had been in isolation for six days for being a close contact of a confirmed case, so this mutation probably emerged de novo, either in the patient himself or in any of the other three members of the cluster after taking their respective samples. Fortunately, the patient had no subsequent close contacts and no new variants belonging to the B.1.1.7 lineage with the E484K mutation have been observed in the daily screenings carried out in our health organisation.

References
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Please cite this article as: Urrutikoetxea-Gutierrez M, Ugalde Zarraga E, Gallego Rodrigo M, Díaz de Tuesta del Arco JL. Aparición de novo de la mutación E484K en una variante del linaje B.1.1.7 de SARS-CoV-2. Enferm Infecc Microbiol Clin. 2022;40:520–522.

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