Evolution of the SARS‐CoV‐2 omicron variants BA.1 to BA.5: Implications for immune escape and transmission

Abstract

The first dominant SARS‐CoV‐2 Omicron variant BA.1 harbours 35 mutations in its Spike protein from the original SARS‐CoV‐2 variant that emerged late 2019. Soon after its discovery, BA.1 rapidly emerged to become the dominant variant worldwide and has since evolved into several variants. Omicron is of major public health concern owing to its high infectivity and antibody evasion. This review article examines the theories that have been proposed on the evolution of Omicron including zoonotic spillage, infection in immunocompromised individuals and cryptic spread in the community without being diagnosed. Added to the complexity of Omicron's evolution are the multiple reports of recombination events occurring between co‐circulating variants of Omicron with Delta and other variants such as XE. Current literature suggests that the combination of the novel mutations in Omicron has resulted in the variant having higher infectivity than the original Wuhan‐Hu‐1 and Delta variant. However, severity is believed to be less owing to the reduced syncytia formation and lower multiplication in the human lung tissue. Perhaps most challenging is that several studies indicate that the efficacy of the available vaccines have been reduced against Omicron variant (8–127 times reduction) as compared to the Wuhan‐Hu‐1 variant. The administration of booster vaccine, however, compensates with the reduction and improves the efficacy by 12–35 fold. Concerningly though, the broadly neutralising monoclonal antibodies, including those approved by FDA for therapeutic use against previous SARS‐CoV‐2 variants, are mostly ineffective against Omicron with the exception of Sotrovimab and recent reports suggest that the Omicron BA.2 is also resistant to Sotrovimab. Currently two new Omicron variants BA.4 and BA.5 are emerging and are reported to be more transmissible and resistant to immunity generated by previous variants including Omicron BA.1 and most monoclonal antibodies. As new variants of SARS‐CoV‐2 will likely continue to emerge it is important that the evolution, and biological consequences of new mutations, in existing variants be well understood.

Impact of reinfection with SARS-CoV-2 Omicron variants in previously infected hamsters

“…Plasma from convalescent human cases and from individuals who had been vaccinated against SARS-CoV-2 exhibited marked reductions in neutralizing activity against Omicron than against the ancestral SARS-CoV-2 (22)(23)(24)(25)(26). Multiple lineages of the Omicron variants have emerged including BA.1, BA.2, BA.3, BA.4 and BA.5, with the dominant strain being replaced by an emerging variant (27). Initially, BA.1 was the most prolific sublineage detected worldwide; however, BA.2 is overtaking BA.1 as the dominant variant and now BA.…”

“…Initially, BA.1 was the most prolific sublineage detected worldwide; however, BA.2 is overtaking BA.1 as the dominant variant and now BA. 5 has replaced (27). In human cases, lower neutralizing antibody titers against the BA.4 and BA.5 subvariants than against the BA.1 and BA.2 subvariants suggest that the Omicron variant is continuing to evolve with increasing capacity for neutralization escape (28).…”

UB-612 Multitope Vaccine Targeting SARS-CoV-2 Spike and Non-Spike Proteins Provides Broad and Durable Immune Responses

“…BA.2 exhibits a 1.3- to 1.5-fold higher transmissibility and a 1.3-fold immune escape than BA.1 (16, 19), consistent with the finding that BA.1-immune sera neutralizes BA.2 with lower titers by a factor of 1.3 to 1.4 (20) and that BA.2 reinfection can occur after BA.1 (21). BA.4/BA.5 are more transmissible and resistant to BA.1/BA.2-immunity and monoclonal antibodies (1, 2). While BA.2 vs. BA.1 (19) and BA.4/BA.5 vs. BA.2 (22) display greater cell-to-cell fusion, they do not make infected people sicker nor change the fundamental pandemic dynamics.…”

“…The SARS-CoV-2 Omicron lineage has swept the globe with a rapid succession of dominating subvariants from BA.1, BA.2 and to the current BA.5 that takes up more than 90% infection cases with overriding edges in transmissibility and neutralizing antibody escape (1)(2)(3)(4)(5)(6)(7). Relative to Delta variant, Omicron BA.1 does not require fusion co-receptor TMPRSS2 for cell entry; instead, cells engulf it and land intracellularly through endosomes (8,9).…”

Effectiveness of a Precise Control Strategy against the COVID-19 Omicron BA.5 Variant in Macao

“…One article review [2] concluded that the Omicron variant causes mild, clinical symptoms but is more infectious than earlier variants. The spread of Omicron was important implications, might require urgent public health interventions to limit transmission, and reduced morbidity [3], especially in crowded region. Approximately 86.6% of the population in Macao completed at least two doses of COVID-19 vaccination [4], but immune escape of the Omicron variant resulted in reduced efficacy of existing vaccines and an increased risk of reinfection [5] coupled with treatment and detection failures [6].…”