The recently identified variant of Omicron BA.4.6a candidate to displace BA.4 and BA.5 as the dominant variant, is a recombinant-type mutation, which occurs when two variants that infect the same person form a new genetic mutation that is associated with immune evasion, therefore it would be more transmissible, but not more serious.
The Omicron variant, already known since it was detected in November 2021, belongs to the nomenclature lineage Pango B.1.1.529), classified as a variant of concern (VOC) by the World Health Organization (WHO) is divided into the following sublineages since its appearance in South Africa: BA.1, BA.1.1, BA.2, BA.3, BA.4 and BA.5.
BA.4.6 is a sublineage of the BA.4 variant of Omicron, a scientific “alias” for B.1.1.529.4.6.1, which has been found mainly in the United Kingdom, the United States, and Germany. Viruses of this sublineage contain a specific mutation in a molecular receptor that has been found before in other variants of interest, that is, those that are monitored once detected to see how they evolve and are tracked and monitored based on data analysis of sequences.
In particular, the Ómicron sublineage BA.4.6 has a mutation at a known antigenically significant site (S:R346T) and an apparent small growth advantage compared to BA.5.
The subvariant BA.4.6 has been designated on September 1 after notification from the United Kingdom Health Security Agency (UKSHA) following its identification on August 15 as a result of surveillance monitoring and preliminary data reported. by the University of Oxford.
The BA.4.6 sublineage. it represented in August, when it detected, approximately 3.3% of the samples of cases notified in the United Kingdom and 9% in the United States. The US Centers for Disease Control and Prevention (CDC) believe that, based on predictive models that can be extrapolated, BA.4.6 could be displacing BA.4 in the United States and there are predictive studies that consider that it will over time others such as the BA.5 or BA.2.75 in Europe, North America and the Middle East while BA.2.75 would take the place of BA.5 in Asia and Oceania.
A lineage is a genetically closely related group of virus variants derived from a common ancestor. A variant has one or more mutations that differentiate it from other variants of SARS-CoV-2, while a recombinant variant such as BA.4.6 is generated from the combination of genetic material from two different variants. Unsurprisingly, multiple variants of SARS-CoV-2 that emerge during the natural evolution of the virus have been documented and constantly monitored during the pandemic.
However, this “shift in the incidence of variants” does not have to imply a worse evolution of the pandemic given the high levels of hybrid immunity due to vaccination or previous infection.
The latest Omicron sublineages best known to the general public are BA.4 and BA.5, identified for the first time in South Africa earlier this year, which in turn were 10% more transmissible than BA.2 due to their ability to to partially evade immunity by vaccination or previous infection (including previous BA.1 infection).
However, after several months as dominant variants due to their greater capacity for transmission and evasion of the immune response, there is no evidence that these sublineages, although more transmissible, are more serious than their wild-type antecedents, alpha, beta and gamma, which caused the vast majority of serious cases and deaths.
The variants that are being monitored, as is the case with BA 4.6, do not a priori represent a significant or immediate risk to the public. However, it is likely to have a potential effect on existing treatments, perhaps more severe symptoms or greater transmission capacity.
The multiple lineages and sublineages of variants of concern under surveillance fall under Omicron unless there is sufficient evidence that the characteristics of the virus are substantially different from the variant of concern to which they belong. If this evidence emerges, the WHO decides whether the designation of the emerging variant justifies the WHO giving it a different name, something that has not happened so far.
The researchers point out that the new variant, being an Ómicron sublineage, would respond in principle to the three-dose vaccine regimen, although the pseudovirus neutralization tests carried out on BA.4.6 show that the neutralization titers are reduced by half compared to the response of BA.4 or BA.5 to a triple dose of the Pfizer BNT162b2 vaccine, the CDC notes.
But its apparent lower response to vaccines is not something intrinsic to a greater danger of this variant, but rather the response to a vaccine or treatment can occur with other variants. For example, one of the anticovid monoclonal antibodies, sotrovimab, has lost its initial efficacy due to the BA.2 sublineage, for which the FDA has withdrawn its authorization, prioritizing Paxlovid and remdesivir in patients at risk with mild to moderate Covid. , or bebtelovimab if there is an indication to use an antibody.
Mutation, lineage and variants
Viruses like SARS-CoV-2 they continually evolve as changes to the genetic code (caused by genetic mutations or viral recombination) occur during genome replication.
To conduct local outbreak investigations and understand national trends, scientists compare genetic differences between viruses to identify variants and how they are related to each other.
Mutation: A mutation refers to a single change in the genetic code of a virus. They occur frequently and there are many under scrutiny, but only sometimes do the characteristics of the virus change.
Lineage: A lineage is a group of viruses closely related to a common ancestor: SARS-CoV-2, which has many lineages, all of which cause Covid-19.
Variant: A variant is a viral genome (genetic code) that may contain one or more mutations. In some cases, public health organizations may designate a group of variants with similar genetic changes, such as a lineage or group of lineages, as Variant Under Control (VBM), Variant of Concern (VOC), or Variant of interest (VOI) due to shared attributes and characteristics that may require public health action.
Recombinant variant: The genomes of two variants that have infected a person at the same time are combined during the viral replication process by exchanging entire pieces of genetic material to form a new variant different from both parental lineages.
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