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.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349777

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

Recombination is a common evolutionary tool for RNA viruses, and coronaviruses are no exception. We review here the evidence for recombination in SARS-CoV-2 and reconcile nomenclature for recombinants, discuss their origin and fitness, and speculate how recombinants could make a difference in the future of the COVID-19 pandemics.

/pdf/recombination-in-coronaviruses-with-a-focus-on-sars-cov-2-1kn1h3n8.pdf

Recombination in Coronaviruses, with a Focus on SARS-CoV-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581791

Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination

The world has not yet completely overcome the fear of the havoc brought by SARS-CoV-2. The virus has undergone several mutations since its initial appearance in China in December 2019. Several variations (i.e., B.1.616.1 (Kappa variant), B.1.617.2 (Delta variant), B.1.617.3, and BA.2.75 (Omicron variant)) have emerged throughout the pandemic, altering the virus’s capacity to spread, risk profile, and even symptoms. Humanity faces a serious threat as long as the virus keeps adapting and changing its fundamental function to evade the immune system. The Delta variant has two escape alterations, E484Q and L452R, as well as other mutations; the most notable of these is P681R, which is expected to boost infectivity, whereas the Omicron has about 60 mutations with certain deletions and insertions. The Delta variant is 40–60% more contagious in comparison to the Alpha variant. Additionally, the AY.1 lineage, also known as the “Delta plus” variant, surfaced as a result of a mutation in the Delta variant, which was one of the causes of the life-threatening second wave of coronavirus disease 2019 (COVID-19). Nevertheless, the recent Omicron variants represent a reminder that the COVID-19 epidemic is far from ending. The wave has sparked a fervor of investigation on why the variant initially appeared to propagate so much more rapidly than the other three variants of concerns (VOCs), whether it is more threatening in those other ways, and how its type of mutations, which induce minor changes in its proteins, can wreck trouble. This review sheds light on the pathogenicity, mutations, treatments, and impact on the vaccine efficacy of the Delta and Omicron variants of SARS-CoV-2.

/pdf/the-delta-and-omicron-variants-of-sars-cov-2-what-we-know-so-1numhd8f.pdf

The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far

Abstract From December 2021-February 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and developed an unbiased bioinformatics method for the detection of co-infections involving genetically distinct SARS-CoV-2 lineages. Applied on 21,387 samples collected between December 6, 2021 to February 27, 2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Among the 53 co-infected patients, a total of 21 patients (39.6%) were not vaccinated. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants. 

/pdf/detection-and-prevalence-of-sars-cov-2-co-infections-during-3cxrr1rl.pdf

Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France

The rapid emergence of new SARS-CoV-2 variants raises a number of public health questions including the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to better understand patterns of transmission and possible load on healthcare resources. Next-Generation Sequencing (NGS) is the primary method for detecting and tracing the emergence of new variants, but it is expensive, and it can take weeks before sequence data is available in public repositories. Here, we describe a Polymerase Chain Reaction (PCR)-based genotyping approach that is significantly less expensive, accelerates reporting on SARS-CoV-2 variants, and can be implemented in any testing lab performing PCR. Specific Single Nucleotide Polymorphisms (SNPs) and indels are identified that have high positive percent agreement (PPA) and negative percent agreement (NPA) compared to NGS for the major genotypes that circulated in 2021. Using a 48-marker panel, testing on 1,128 retrospective samples yielded a PPA and NPA in the 96.3 to 100% and 99.2 to 100% range, respectively, for the top 10 most prevalent lineages. The effect on PPA and NPA of reducing the number of panel markers was also explored. In addition, with the emergence of Omicron, we also developed an Omicron genotyping panel that distinguishes the Delta and Omicron variants using four (4) highly specific SNPs. Data from testing demonstrates the capability to use the panel to rapidly track the growing prevalence of the Omicron variant in the United States in December 2021.

A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron

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Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination

A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron