Introduction of Brazilian SARS-CoV-2 484K.V2 related variants into the UK

While the new UK SARS-CoV-2 variant (B.1.1.7/ VOC-202012/01) continues to cause a large number of new COVID-19 cases in the UK,¹ focus in the media has currently shifted to the potential for import of other new variants that may also be more infectious and/or demonstrate immune or vaccine escape based on mutations in the S protein.

Cases of such a variant from South Africa (B.1.351/ 501Y.V2) have already been reported in the UK,² but two new variants from Brazil are currently receiving more attention. Both of these Brazilian variants have their origins in the B.1.1.28 clade but the similarities have led to confusion in the general press, with reports that one variant has been detected in the UK but not the other (BBC News, https://www.bbc.co.uk/news/health-55676637). With regards to nomenclature, the aforementioned B.1.1.7, B.1.351 and the B.1.1.28 lineages refer to those assigned using the pangolin tool (https://cov-lineages.org) and, in the case of the UK and South African variants, they are also referred to by the name assigned by local researchers. Different characterisation is assigned by Nextstrain and a global system has yet to be agreed upon.³

The B.1.1.28 clade has been a significant circulating lineage within Brazil and likely originated in February 2020.⁴ The first variant referred to contains the S protein mutation E484K and was first detected in sequences from patients in Rio de Janeiro state collected in October 2020 but based on phylogenetic analysis the variant likely originated in July 2020.⁵ This 484 K.V2 variant has since spread to multiple other countries including: England, Singapore, the USA, Norway, Argentina, Denmark, Ireland and Canada (sequences coloured blue and purple in the Fig. 1 ). The E484K mutation in particular is of interest due to evidence that it may allow immune escape.^{6 , 7}

Fig. 1.

A maximum likelihood tree of the Brazilian B.1.1.28 lineage demonstrating sequences imported to the UK. The Wuhan SARS-CoV-2 reference sequence is used as the root. Sequences for the UK (VOC202012.01) (pink) and South African (501Y.V2) (green) variants are also shown for comparison. The 28-AM-II/P.1 variants (red) are shown with the 484 K.V2 variants from England (blue) and from other countries (purple). Please see main text for additional details. Full genome SARS-CoV-2 sequences were downloaded on 19 January 2021 from GISAID (https://www.gisaid .org/), aligned using MAFFT: https://mafft.cbrc.jp/alignment/software/ and manually edited using BioEdit v7.2.5. Phylogenetic tree construction was performed using FastTree v2.1.11, with Shimodaira-Hasegawa-like local branch supports, and displayed using FigTree v1.4.4. We gratefully acknowledge and thank all the teams and laboratories that have deposited these sequences into GISAID to make this analysis possible (see Supplementary Acknowledgements file attached). Note that this phylogenetic tree is only intended to be illustrative and not comprehensive.

Further study is needed to demonstrate whether these mutations will impact on immune, or indeed vaccine, response. Differences in clinical severity of COVID-19 with these variants has not thus far been detected. Of note, the E484K mutation exists in the South African variant (coloured green in the Fig. 1) but not in the UK variant (coloured pink in the Fig. 1). This E484K (484 K.V2) variant has been detected in UK imports since November 2020 with likely onward transmission (coloured blue in the Fig. 1). For the alignment, all UK sequences identified as B.1.1.28 lineage on GISAID were analysed with additional B.1.1.28 and 484 K.V2 sequences for context. Duplicate sequences were removed for the final phylogenetic tree and sequences for the UK and South African variants added along with the Wuhan SARS-CoV-2 reference sequence.

The second variant of note became widely reported following an announcement by the Japanese National Institute of Infectious Diseases following detection in Brazilian travellers to Japan⁸ which, in addition to the E484K mutation, also has L18F, T20N, P26S, D138Y, R190S, K417T, N501Y, D614G, H655Y, T1027I and V1176F mutations in the S protein (NIID, https://www.niid.go.jp/niid/en/2019-ncov-e/10108-covid19–33-en.html) and designated as B.1.1.248 (coloured red in the Fig. 1). This variant likely arose from the Amazonas (AM) region of Brazil. Hence, Naveca et al.⁸ designated this variant as 28-AM-II. In addition, another variant which shares the K417T, E484K, N501Y mutations also arose independently from this B.1.1.28 lineage from Amazonas, which is designated as 28-AM-I.⁸ Both these variants have also been assigned a designation of P.1 variant, as part of the B.1.1.28 nomenclature.⁹ These Brazilian variants 28-AM-I and 28-AM-II (P.1) may have enhanced transmissibility similar to the South African variant as they share a similar pattern of mutations (N501Y, E484K, K417N/T).²

Note that a sequence from Brazil and South Korea (coloured orange/brown in the Fig. 1) also cluster with the 28-AM-II sequences, but both lack the R190S mutation. In addition, this Brazilian sequence (EPI-ISL-804,824) also has an ‘N’ ambiguity code at the H655 position, which accounts for its additional distance within this cluster.

Neither of these two 28-AM-I and 28-AM-II (P.1) Brazilian variants has yet been detected within existing UK sequences to date, unlike the E484K (484 K.V2) variant (coloured blue in the Fig. 1) which has received a provisional designation of P.2 (coloured blue in the Fig. 1) to differentiate it from the P.1 (28-AM-I, 28-AM-II) variants (coloured red in the Fig. 1).¹⁰ Unfortunately, this designation may cause more confusion as not all the E484K mutants are within a separate group as demonstrated in our phylogenetic analysis (the one England sequence coloured turquoise in the Fig. 1) and confirmed elsewhere.¹⁰

The UK government's response on detection of these non-UK variants was to first restrict travel from South Africa and then Brazil and related travel destinations such as Portugal. Subsequently ‘travel corridors’ from countries with low infection rates were closed to attempt to reduce the potential for the import of other new variants (UK government advice, 2021, https://www.gov.uk/guidance/coronavirus-covid-19-travel-corridors).