The Most Infectious Coronavirus Variant Ever: What is XBB.1.5 (Kraken)?
A new variant of SARS-CoV-2 is causing major concern over potential surges in COVID-19 infections and reinfections at the dawn of the new year. Since its initial emergence in the United States in early December, the Omicron XBB.1.5 variant has rapidly grown dominant and spread around the globe. Due to its apparently superior transmissibility, the Omicron XBB.1.5 variant has been nicknamed the “Kraken variant”. Although the data on the Omicron XBB.1.5 strain is scarce, it is known to be a descendant of the Omicron XBB subvariant, which is a cross between Omicron BA.2.75 and BA.2.10.1. So, what else do we know about the newest SARS-CoV-2 variant of concern? Read along to learn more about the Omicron XBB subvariant, its mutational profile, infectivity, pathogenicity, and implications for the future of the pandemic.
How common is the Omicron XBB.1.5 variant?
According to the genomic surveillance system of the Centers for Disease Control and Prevention (CDC), the Omicron XBB.1.5 variant has jumped from causing 1% of all cases in the US to over 40% since the start of December. In the northeastern states, the same figure has surpassed 70%. Since its emergence, the Omicron XBB.1.5 variant has spread to more than 30 countries, including the United Kingdom, Canada, Denmark, Germany, Austria, France, Israel, and Australia. Although the proportion of infections caused by XBB.1.5 remains low outside of the United States, health authorities are warning that the variant could be much more widespread due to the removal of testing measures around the world.
Why is the Omicron XBB.1.5 variant spreading so rapidly?
The World Health Organization (WHO) has recently identified the Omicron XBB.1.5 as the most transmissible strain detected. Indeed, the adequate reproductive number of the variant, which refers to the number of new infections expected to be caused by each infected person, is estimated to be around 1.6. This figure is approximately 40% higher than its next closest competitor. Its evasive immune features are likely to be among the factors responsible for the growth advantage of the Omicron XBB.1.5. As exemplified by Wang et al. (2022), several studies have demonstrated the impairment of neutralization antibodies against infections with the Omicron XBB and XBB.1 strains. The Omicron XBB.1.5 variant appears to share these immune-evasive features observed in Omicron XBB and XBB.1. Therefore, the Omicron XBB.1.5 variant is expected to have an enhanced ability to evade neutralizing antibodies even in people who have completed primary vaccination, received boosters, or experienced a previous breakthrough Omicron infection.
In addition to its evasive immune features, it has been found that the Omicron XBB.1.5 variant demonstrated a much higher level of affinity to ACE2 due to the mutation known as F486P. On the one hand, this mutation has reduced the effectivity of neutralizing antibodies and enhanced the ability of the virus to evade immune defenses by altering a part of the virus that is a key target for many vaccination-induced and infection-induced antibodies. On the other hand, it allowed the strain to bind more tightly to ACE2, which is a key receptor for SARS-CoV-2. This, in turn, has increased the transmissibility of the strain and enabled it to enter human cells with more ease. Thus, the Omicron XBB.1.5 variant not only demonstrates a level of immune evasion similar to the Omicron XBB and XBB.1 subvariants, but it also avoids the deficiency observed in these strains by simultaneously driving up its infectivity. Finally, virologists and epidemiologists also argue that it may be challenging to differentiate the advantages offered by the mutational profile of the strain and good timing. Indeed, during the holiday season, during which people commonly travel, socialize, and gather indoors, infections are more likely to spread regardless of whether it is influenza, COVID-19, or RSV.
Does the Omicron XBB.1.5 variant cause more severe disease?
According to the World Health Organization (WHO), data on the severity of disease caused by the Omicron XBB.1.5 variant is currently insufficient. Indeed, while the US is experiencing a surge in hospitalizations, the agency has reported that the current increase in hospitalizations cannot be reliably attributed to the Omicron XBB.1.5 variant, given the circulation of many other respiratory viruses. So far, experts have observed no indication of increased disease severity or altered clinical presentation. Thus, the symptoms and pathogenicity of infections caused by the Omicron XBB.1.5 variant is expected to be comparable to those caused by other strains of the Omicron variant. Although increased transmissibility and consequent waves of infection remain a major concern, experts argue that our vaccines and treatments can continue to prevent severe symptoms, hospitalization, and death.
Can the Omicron XBB.1.5 variant cause future waves of COVID-19?
It remains unclear whether the Omicron XBB.1.5 variant will drive major outbreaks around the world. The original XBB variant has caused waves of infection in some countries, such as Singapore and India. Omicron XBB.1.5, on the other hand, is suspected to be at least partly responsible for the rise in COVID-linked hospitalizations in the US. As the new strain spreads and circulates around the world, experts anticipate some increase in COVID-19 cases. Still, in sufficiently vaccinated populations, the variant is not expected to cause a significant increase in the incidence of severe disease, hospitalization, and death.
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Davis-Gardner, M. E., Lai, L., Wali, B., Samaha, H., Solis, D., Lee, M., Porter-Morrison, A., Hentenaar, I. T., Yamamoto, F., Godbole, S., Liu, Y., Douek, D. C., Lee, F. E. H., Rouphael, N., Moreno, A., Pinsky, B. A., & Suthar, M. S. (2022). Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster. New England Journal of Medicine. https://doi.org/10.1056/nejmc2214293
Wang, Q., Iketani, S., Li, Z., Liu, L., Guo, Y., Huang, Y., Bowen, A. D., Liu, M., Wang, M., Yu, J., Valdez, R., Lauring, A. S., Sheng, Z., Wang, H. H., Gordon, A., Liu, L., & Ho, D. D. (2022). Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. https://doi.org/10.1101/2022.11.23.517532