Omicron XBB.1.5: Heightened Transmissibility, Infectivity, and Immune Resistance

COVID-19 has loomed large for the last 3 years, but our knowledge and treatments have advanced far beyond where we were in those early days of the pandemic.

Unfortunately, the virus has advanced as well. COVID-19 continues to mutate, and its latest iteration, the Omicron XBB.1.5 subvariant, has quickly overtaken the other circulating strains.

XBB.1.5 was first detected in October 2022, and it has since become the most prevalent variant in the United States. The latest genomic surveillance data from the US Centers for Disease Control and Prevention (CDC) estimates XBB.1.5 is responsible for 89.5% of new infections.

A recent study, published in The Lancet Infectious Diseases, conducted a thorough analysis of this latest variant of concern. The investigators believe a comprehensive understanding of XBB.1.5’s virological characteristics is needed to sustain global health.

Like its Omicron predecessor BQ.1, the XBB lineage can be characterized by amino acid substitutions in its spike protein that increase viral fitness. XBB is the recombinant of 2 highly diversified BA.2 lineages, variants of concern which have since diminished to causing less than 0.1% of new US COVID-19 cases.

The investigators found the relative effective reproduction number (Re) of XBB.1.5 is 1.2 times greater than that of its paternal sublineage, XBB.1. Additionally, the dissociation constant value of XBB.1.5’s spike receptor-binding domain from the human ACE2 receptor is 4.3 times lower than that of XBB.1. “These results suggest that XBB.1.5 exhibits a remarkably strong affinity to the human ACE2 receptor,” the study authors wrote.

Their findings led the investigators to conclude that XBB.1.5 is the most successful XBB lineage. XBB.1.5 has an increased binding affinity to the ACE2 receptor “without compromising its remarkable immune resistance.”

COVID-19 vaccination remains an effective strategy, protecting against infection and severe, symptomatic disease. The newly updated bivalent COVID-19 boosters are particularly effective against emerging variants. However, surveillance is vital to ensure new variants do not develop resistance to our vaccines.

“Because the Omicron XBB.1.5 variant can spread more rapidly than previous variants and has a potential to cause the next epidemic surge, we should carefully monitor it to safeguard public health,” said study author Kei Sato, a professor in the University of Tokyo’s Division of Systems Virology and Institute of Medical Science.