COVID-19: XBB.1.5 – CH.1.1 – CA.3.1 Variants Have Increased Fusogenicity Than BA.2


A new study led by researchers from Ohio State University-USA has found that the current SARS-CoV-2 subvariants that are predominant in circulation in various parts of the world ie XBB.1.5 alias Kraken, CH.1.1 and CA.3.1 are far more fusogenic than the BA.2 variant with the potential to increase the risk of disease severity in those infected.

The study findings were published on a preprint server and are currently being peer reviewed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, continues to circulate across the globe while rapidly evolving.

The beginning of 2022 was marked by the emergence of Omicron BA.1/BA1.1 variant, establishing a turning point in the pandemic with decreased pathogenicity1–5, increased transmissibility2, and enhanced immune escape6–13.

During 2022, the prototype Omicron variant has given rise to numerous subvariants, with many displaying even higher extents of immune escape9,14–22, endangering the efficacy of vaccination efforts.

Following a few months of BA.5 dominance in the summer of 2022, a highly immune evasive16,23,24 Omicron subvariant, i.e., BQ.1.1, became the most prevalent in the United States; however, it is now being quickly supplanted by a new subvariant, XBB.1.525.

The XBB lineage was initially discovered in India in mid- August of 2022, resulting from a recombination event between two BA.2 lineages titled BA. and BA.2.7526. The emergence of this subvariant raised much alarm, as it has brought together a number of mutations in the spike (S) protein with established immune evasion functions, including R346T, G446S and F486S (Fig. 1A)15.

Importantly, the efficacy of monoclonal antibody treatments24, both monovalent23 and bivalent16,27 vaccination strategies, as well as immunity stimulated by infection23,27, are all less effective against XBB. Recently, XBB has acquired two more mutations in the S protein, including G252V (XBB.1) and G252V+S486P (XBB.1.5) (Fig. 1A).

The influence of these mutations on XBB.1 and XBB.1.5 is currently unknown, though mutations at residue F486, such as F486V, F486I, F486S, have been recurring among prior Omicron subvariants26, representing a critical evolutionary hotspot28. Given the rapid growth of XBB.1.5 in circulation in the United States and other parts of the world (Fig. 1B and Fig. S1A), it is crucial that we understand its impact on current public health measures.

In addition to BQ.1, BQ.1.1 and XBB subvariants, two other Omicron subvariants, CH.1.1 and CA.3.1, have also drawn attention. CH.1.1 emerged in Southeast Asia in November of 2022 and now accounts for more than 25% of infections in some parts of UK and New Zealand; it has caused alarm due to the appearance of the L452R mutation in the S protein29, which previously appeared in the more pathogenic Delta variant and highly transmissible BA.4/5 variants18,30,31.

CA.3.1 emerged in the United States in December of 2022 and also carries this critical L452R mutation29. In this study, we investigate aspects of S protein biology of XBB.1.5, CH.1.1 and CA.3.1 in comparison to their parental variants, including entry into host cells, surface expression, fusogenicity,

and processing. Most critically, we determine and compare their sensitivity to neutralizing antibodies stimulated by either bivalent or monovalent mRNA vaccination and previous infection (BA.5 wave), alongside with ancestral variants D614G, BA.2, and BA.2.75.2 as well as currently dominating variant BQ.1.1.




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