Molecular Epidemiology of the Norwegian SARS-CoV-2 Delta Lineage AY.63

Abstract

Extensive genomic surveillance has given great insights into the evolution of the SARS-CoV-2 virus and emerging variants. During the summer months of 2021, Norway was dominated by the Pango lineage AY.63 which is a sub-lineage of the highly transmissible Delta variant. Strikingly, AY.63 did not spread in other countries to any significant extent. AY.63 carried a key mutation, A222V, in the spike protein, as well as the deletion of three residues in nsp1. Although these mutations are close to functionally important areas, we did not find any evidence that they induced higher fitness compared to other Delta lineages. This variant was introduced to Norway at a time when there were low levels of SARS-CoV-2 and contact-reducing measures were relaxed, which probably explains why the lineage rose so quickly. Furthermore, we found that the lack of imports of AY.63 from other countries probably led to the eventual demise of the lineage in Norway.

Keywords: AY.63; Delta; Norway; SARS-CoV-2.

Figure 1

Spread of AY.63 in Norway, 2021. (A) Proportions of the B.1.1.7, AY.63, and the five most common Pango lineages circulating in Norway between weeks 23–48, 2021. “Other” lineages (colored grey) contain all other circulating lineages (including a few Omicron cases). The black dashed line shows the percent of people (<18 years) who had received two doses of vaccination against SARS-CoV-2. The black dotted line shows the numbers of positive SARS-CoV-2 cases in Norway (plotted on the secondary y-axis). Week numbers and months of 2021 are shown on the x-axis. (B) Number of sequenced samples of AY.63 colored by Norwegian county. The X-axis is the same as in figure (A). The map was adapted from Wikipedia.org (accessed on 10 October 2022). (C) Cumulative cases of sequenced samples of AY.63 and the five other most frequent Delta lineages in weeks 23–48.

Figure 2

Phylogeny of AY.63. Phylogenetic analysis of AY.63 with a selection of the closest non-AY.63 Delta sequences as the outgroup (not shown). The tree on the left has the branch tips arranged according to sample date, with the internal nodes positioned on their inferred dates according to TreeTime; while on the right, the branch tips are arranged according to the genetic divergence from the root of the tree. Norwegian samples are colored according to region, and the non-Norwegian samples are indicated with grey circles.

Figure 3

Phylogeny of the Delta lineage. (A) Phylogenetic analysis of Delta with the Pango lineage AY.63 and NextClade clade annotations indicated. The strains carrying the characteristic genetic signatures for AY.63, spike A222V (left tree), and ORF1a 141–143 deletions (right tree) are colored yellow. (B) The number of sequences with Pango lineage AY.63 published in GISAID drawn on their country of origin. In addition to the countries visualized here, there is also one sequence sampled from the USA published in GISAID. The map was adapted from Wikipedia.org, accessed on 10 October 2022.

Figure 4

Lineage dynamics. Cumulative average pairwise SNP distances plotted over time for the Norwegian AY.63 sequences and the most frequent co-circulating lineages. To the right of each graph is the Pango lineage nomenclature for each of the lineages indicated with the estimated number of imports into Norway in parenthesis.

Figure 5

Genetic characteristics of AY.63. Overview of spike and ORF1a mutations shared between the most common Delta variants in week 23–48.

Figure 6

Structure analysis of AY.63 spike mutations. (A) Top and side-view of the spike protein where each subunit is colored differently (in the homotrimeric structure) with the mutations for AY.63 highlighted. (B) The A222V mutation visualized where alanine residue is to the left and valine on the right side.