Covid. ECDC: “The Kraken sub-variant could increase cases in the EU”. But the vaccine appears to protect to a similar extent to the other Omicrons

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This is what the ECDC reports today, citing a Chinese preprint that analyzed the new sub-variant in strong diffusion in the USA. However, cases could indeed increase, but not within the next month “since the variant is currently present only at very low levels”. However, there is not enough information available to evaluate “any changes in the severity of the infection associated with the variant”. Kraken has a Ser486Pro mutation on the spike protein, “a rare 2-nucleotide substitution compared to the ancestral strain”. The mechanism behind the rapid transmission of XBB.1.5, especially the impact of Ser486Pro, “requires immediate investigation.”

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There is a risk that the Kraken (XBB.1.5) variant could have “a growing effect on the number of Covid cases in the EU/EEA, but not within the next month, as the variant is currently only present at very low levels”. At the moment, however, there is not enough information available to evaluate “any changes in the severity of the infection associated with the variant”.

The ECDC takes stock of the situation on the variant that could become the dominant one in the United States in the coming weeks. The US CDC reports a time to doubling the percentage of XBB.1.5 of 9 days and the US CDC nowcast system estimates the current percentage of the variant at around 27.6% in the US (95% prediction interval 14, 0-46.5%). “Due to the uncertainty associated with the estimate, it is not yet clear whether the variant will become dominant in the US in the coming weeks. Rapid growth in the US does not necessarily mean that the variant will become dominant in the EU/EEA, as during large differences in the circulation of the variant between North America and Europe have been observed several times during the pandemic”, underlines the ECDC.

In taking stock of the new variant, the ECDC then cites a recent Chinese preprint where it explains how, compared to the XBB (Gryphon) variant, XBB.1.5 (Kraken) has a Ser486Pro mutation on the spike protein, “a rare substitution of 2 nucleotides compared to the ancestral stock”. The mechanism behind the rapid transmission of XBB.1.5, especially the impact of Ser486Pro, “requires immediate investigation,” the study emphasizes.

The preprint also adds that Kraken’s immune escape ability, on people protected by vaccination or previous infection, is “comparable to that of Gryphon, indeed it is slightly weaker”. The monoclonal antibodies Evusheld and Bebtelovimab “failed to neutralize Kraken. Monoclonal S309 is still active but weak against this variant, SA58 has been bypassed while SA55 remains highly effective.” The significant growth advantage of XBB.1.5 compared to XBB.1 is due to having obtained a substantially higher binding affinity with the ACE2 receptor, i.e. the ‘gate’ that the virus uses to enter cells, thanks to the mutation Ser486Pro, while maintaining an extremely high immune evasion capacity.

Also in the preprint it is underlined that it is not currently clear whether “the increase in the binding affinity with the receptor can cause a difference in pathogenicity compared to XBB, which should be investigated immediately”. Furthermore, “the strong affinity to hACE2 could allow XBB.1.5 to acquire additional immune mutations, similar to the evolutionary trend of BA.2.75 (Centaurus), when subjected to substantial immune pressure.” For this reason, the Chinese authors write, “the circulation of XBB.1.5 must be carefully monitored and the development of neutralizing antibodies and effective vaccines against this variant” is urgently needed.

Giovanni Rodriguez

09 January 2023
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