Scientists have observed several Omicron descendants competing for dominance in the transmission of Covid-19 in the United States, with the BQs (BQ.1 and BQ.1.1) currently leading in the competition. However, the US Centers for Disease Control and Prevention’s Covid-19 variant dashboard recently identified a new variant, XBB.1.5, which has rapidly increased in prevalence. Over the past four weeks, the CDC estimates that XBB.1.5 has more than doubled its share of new Covid-19 infections, rising from approximately 4% to 41% of new infections in December. In the Northeast region, XBB.1.5 is believed to be responsible for 75% of new cases. Pavitra Roychoudhury, director of Covid-19 sequencing at the University of Washington School of Medicine’s virology lab, commented that they have not seen a variant grow at such a fast rate in the past few months.
Virologists and epidemiologists believe that the Omicron sublineage has the potential to cause a new surge of Covid-19 cases in the United States, although it is uncertain how severe this increase will be or whether it will result in more hospitalizations. It is worth noting that XBB.1.5 appears to have originated in the United States, specifically in New York and Connecticut, as detected by GISAID (a global initiative to catalog and track coronavirus variants) in late October. This is noteworthy because there has been recent concern that a new threat from Covid-19 could come from the ongoing surge in cases in China.
Trevor Bedford, a professor of computational biology at the Fred Hutchinson Cancer Center in Seattle, noted that XBB.1.5 has a similar growth rate to its cousin BA.5 and estimates that its effective reproductive number, or the number of new infections expected to be caused by each infected person, is around 1.6, which is about 40% higher than its closest competitor. Bedford believes that XBB.1.5 will likely lead to an increase in circulation in the coming weeks, although this increase may not be reflected in the number of reported cases due to more people testing at home and their cases only being counted if they seek medical care and receive a laboratory test to confirm their results. Bedford recommends looking at hospitalizations among vulnerable age groups, such as seniors, as a better indicator of the wave.
XBB.1.5 was created through recombination, which occurs when two descendants of BA.2, the subvariant that caused a small increase in cases in the US in April, exchanged pieces of their genetic code. This resulted in 14 new mutations in the virus’s spike proteins and the creation of a new sublineage called XBB. While XBB caused a wave of cases in Singapore earlier in the year, it did not gain much traction in the United States due to competition with other co-circulating variants that had independently evolved some of the same mutations, making them more evenly matched. Scientists have been closely monitoring XBB and its derivatives.
Dr. David Ho, a professor of microbiology and immunology at Columbia University, recently conducted a laboratory study in which he tested viruses with the spikes of XBB, XBB.1, BQ.1, and BQ.1.1 against antibodies from the blood of individuals who had been infected with Covid-19, vaccinated with the original and new bivalent vaccines, or both infected and vaccinated. His team also tested 23 monoclonal antibody treatments against these new sublineages. The results showed that XBB.1 was the most difficult to neutralize, being 63 times less likely to be neutralized by antibodies in the blood of infected and vaccinated individuals compared to BA.2 and 49 times less likely to be neutralized compared to BA.4 and BA.5. Dr. Ho explained that these variants have a high degree of immune evasion, meaning they are able to avoid being neutralized by the antibodies that have been developed to target them, similar to the original Omicron variant’s ability to evade neutralization by the Covid-19 viruses that preceded it about a year ago.
In addition to its high level of immune evasion, XBB.1.5 also has a mutation at site 486 that allows it to bind more effectively to ACE2, the doorway that the virus uses to enter our cells. This mutation is thought to be contributing to the growth of XBB.1.5. Jesse Bloom, a computational virologist at the Fred Hutchinson Cancer Center, stated in an email that the mutation “is clearly letting XBB.1.5 spread better.”
References: CNN