Follow-up investigation and detailed mutational characterization of the SARS-CoV-2 Omicron variant lineages (BA.1, BA.2, BA.3 and BA.1.1)

Abstract

Aided by extensive protein mutations, the SARS-CoV-2 Omicron (B.1.1.529) variant overtook the previously dominant Delta variant and rapidly spread around the world. It was shown to exhibit significant resistance to current vaccines and evasion from neutralizing antibodies. It is therefore critical to investigate the Omicron mutations trajectories. In this study, a literature search of published articles and SARS-CoV-2 databases was conducted, We explored the full list of mutations in Omicron BA.1, BA.1.1, BA.2, and BA.3 lineages. We described in detail the prevalence and occurrence of the mutations across variants, and how Omicron differs from them. We used GISAID as our primary data source, which provides open access to genomics data of the SARS-CoV-2 virus, in addition to epidemiological and geographical data. We examined how these mutations interact with each other, their co-occurrence and clustering. Our study offers for the first time a comprehensive description of all mutations with a focus on non-spike mutations and demonstrated that mutations in regions other than the Spike (S) genes are worth investigating further. Our research established that the Omicron variant has retained some mutations reported in other SARS-CoV-2 variants, yet many of its mutations are extremely rare in other variants and unique to Omicron. Some of these mutations have been linked to the transmissibility and immune escape of the virus, and indicate a significant shift in SARS-CoV-2 evolution. The most likely theories for the evolution of the Omicron variant were also discussed.

Genomic Diversity of SARS-CoV-2 Omicron Variant in South American Countries

“…Genomic monitoring of SARS-CoV-2 variants in different regions of the world allows understanding of the dynamics and genetic mechanisms of each variant [1], especially in Omicron, that has several mechanisms to promote increased transmission and immune escape [7,11]. Furthermore, this variant has an estimated transmission rate between 5 and 8 [12], which means that Omicron is transmitted rapidly, leading to an increase in the number of associated cases.…”

“…As for BA.2, it is interesting to note the low number of genomes reported so far and the circulation in only a few countries on the continent (Table S1 and Figure 1b) and the minor divergent cluster (Figure 3). Unlike BA.1 and BA.1.1, this lineage has a greater number of unique mutations, mainly in the Spike gene, promoting more effective immune evasion and transmissibility [7][8][9][10][11][12][13]. Moreover, this number of unique mutations might be contributing to the associated divergent clustering for this lineage, which differs from the other clusters that contain the BA.1 and BA.1.1 genomes.…”

“…We analyzed 21,615 high-quality and complete Omicron genomes from South America available in the GISAID database until 28 February 2022 (Table S1). The analysis of these genomes was performed according to the Muñoz et al (2021) and Ramírez et al (2020) schemes [7,8]. These schemes consisted of SARS-CoV-2 lineage typing using the PANGOLIN-v1.9 tool (https://github.com/cov-lineages/pangolin (accessed on 10 May 2022)), and alignment and phylogenetic analysis using the NextClade tool v1.5.4 default command line (https://docs.nextstrain.org/projects/nextclade/en/stable/user/nextcladecli.html (accessed on 10 May 2022)), which performs sequence alignment, variant calling, clade assignment and maximum-likelihood (ML) tree placement.…”

“…This VOC, known as Omicron, harbors a high number of mutations that favor immune evasion, increased transmissibility and decreased vaccine efficiency in preventing infection [5,6]. Moreover, this variant has shown several dispersals and global transmission events [7] associated with the different Omicron sublineages (BA.1, BA.1.1, BA.2 and BA.3). Compared to the sublineages of other VOCs (i.e., Delta), these have unique genomic characteristics that have generated a public health impact [7].…”

“…Moreover, this variant has shown several dispersals and global transmission events [7] associated with the different Omicron sublineages (BA.1, BA.1.1, BA.2 and BA.3). Compared to the sublineages of other VOCs (i.e., Delta), these have unique genomic characteristics that have generated a public health impact [7]. Therefore, surveillance and genomic studies have focused on analyzing these characteristics that have enabled Omicron to create a significant health turmoil.…”