Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

“…The second year of the SARS-CoV-2 pandemic was marked by the repeated emergence of SARS-CoV-2 ‘variants’ with altered antigenicity, and/or enhanced transmissibility. The fifth ‘variant of concern’, Omicron (Pango lineage BA.1), was first detected in Southern Africa 1 and, within a just a month of its initial detection, has rapidly spread across the world comprising the majority of SARS-CoV-2 cases in many countries including the UK 2 . Omicron is marked by a total of 51 mutations across the entire genome including an unprecedented 33 mutations in its Spike glycoprotein gene 1,3 .…”

“…The fifth ‘variant of concern’, Omicron (Pango lineage BA.1), was first detected in Southern Africa 1 and, within a just a month of its initial detection, has rapidly spread across the world comprising the majority of SARS-CoV-2 cases in many countries including the UK 2 . Omicron is marked by a total of 51 mutations across the entire genome including an unprecedented 33 mutations in its Spike glycoprotein gene 1,3 . The resulting large antigenic distance between Omicron and the Wuhan-like Spike protein used in current vaccines 3-9 , correlates with a lower vaccine effectiveness against Omicron and a higher frequency of reinfections 2,10,11 .…”

Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

“…The most prominent viral variant carrying an insertion at RIR1 (the XLI 215:EPE insertion, see Table 1 ) is undoubtedly the emerging VOC omicron (which includes the lineages B.1.1.529, BA.1, BA.2 and BA.3), which, as of January 5 th , 2022, is rapidly outcompeting delta worldwide. Although omicron was first detected on November 8 th , 2021, time-calibrated Bayesian phylogenetic analyses suggest that it might have been spreading undetected in Southern Africa since early October ( Viana et al, 2021 ). The XLI insertion is paired with three small deletions in the spike NTD: (i) Δ69/70 at RDR1, which has been previously suggested to act as a “permissive” mutation to compensate otherwise slightly deleterious immune escape mutations ( Meng et al, 2021 ); (ii) Δ143/144/145 at RDR2, known to fall within a relevant antibody epitope ( McCarthy et al, 2021 ); (iii) Δ212, with unknown functional significance, located close to the RIR1 site.…”

Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response

“…Omicron (B.1.1.529) is a new variant of concern (VOC) of the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. Since its detection in South Africa in November 2021 (1), Omicron has rapidly spread in all countries where it was introduced, indicating elevated infectivity and a certain resistance to pre-existing immunity (2). These features are due to an unprecedented number of mutations that are distinguishing Omicron from the original coronavirus that emerged in Wuhan, China, at the end of 2019, as well as from the subsequently appearing VOCs like e.g.…”