Omicron: Drifting and Shifting

January 10, 2023

In September of 2022, we blogged about Omicron's BA.2.75 subvariant, citing:

As BA.2.75 and other subvariants BA.5 and BA.4 all try to outcompete one another, a recombinant strain may emerge due to multiple variants infecting the same person simultaneously. This allows the variants to interact during replication by mixing their genetic materials in the human body to survive.

Analyzing SARS-CoV-2 patterns and data, we knew it was only a matter of time that BA.2.75 would find its ideal match to mix with and cause another wave of infection. As predicted, BA.2.75 merged with BA.2.10.1 and spawned XBB/XBB.1.5, street names Gryphon and Kraken.  

With 14 mutations in addition to those found in BA.2, including 9 in the receptor-binding domain (RBD) and 5 in the N-terminal domain (NTD), the XBB sublineage is comparable to the antigenic drift made by the initial Omicron variant from its predecessors one year ago.

Antigenic drift
refers to the gradual change in the antigenicity of viral proteins, driven by antibody selection of escape mutants (the mutated antigen 'drifts' from the original variant). Typically only observed in viruses like influenza, an antigenic shift is an abrupt change in one or both surface antigens resulting in an entirely new variant. The XBB sublineage and its alarming antibody-evading properties mark a significant antigenic drift and potential shift in SARS-CoV-2.

Some hypothesize that although recombination events are a hallmark of coronaviruses, the Omicron antigenic shift may be from prolonged viral replication in the context of an inadequate immune response —facilitating further mutations. This begs the question, how many humans have an "inadequate immune response"?

With XBB and BQ sublineages fighting for dominance, a new recombinant strain and/or a novel variant could crop up. The real risk, however, is that two to three significant antigenic shifts could render existing molecular testing assays insufficient, rapid antigen tests useless, and mAbs and non-sterilizing vaccines ineffective.

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