TAG-VE statement on Omicron sublines BQ.1 and XBB

This decision will be reviewed regularly. If there are any significant developments that require a change in public health strategy, WHO will immediately alert Member States and the public.

XBB*

XBB* is a recombinant of BA.2.10.1 and BA.2.75 strains. As of epidemiological week 40 (October 3 to 9), from sequences submitted to GISAID, XBB* has a global prevalence of 1.3% and has been detected in 35 countries. TAG-VE discussed available data on the benefits of growing this medium and some early evidence on clinical severity and risk of reinfection from Singapore and India, as well as information from other countries. There has been a broad increase in the prevalence of XBB* in regional genomic surveillance, but it is still not consistently associated with an increase in new infections. Although further research is needed, current data do not suggest significant differences in disease severity for XBB* infections. However, there is early evidence to suggest a higher risk of reinfection compared to other Omicron circulating media. Cases of reinfection were primarily limited to those with initial infection in the pre-Omicron era. So far, there are no data to support escape from recent immune responses induced by other Omicron lines. Whether increased immune escape of XBB* is sufficient to trigger new waves of infection appears to depend on the regional immune landscape, which is influenced by the size and timing of previous Omicron waves, as well as the coverage of vaccination against COVID-19.

BQ.1*

BQ.1* is a sublineage of BA.5, which carries spike mutations at some key antigenic sites, including K444T and N460K. In addition to these mutations, sublineage BQ.1.1 carries an additional spike mutation at a key antigenic site (ie, R346T). As of epidemiological week 40 (October 3 to 9), according to sequences submitted to GISAID, BQ.1* has a prevalence of 6% and has been detected in 65 countries. Although there are no weight or immune escape data from human studies, BQ.1* shows a significant growth advantage over other circulating Omicron sublines in many settings, including Europe and the US, and thus warrants careful monitoring. It is likely that these additional mutations conferred an immune escape advantage over other circulating Omicron substrates, and therefore a greater risk of reinfection is a possibility that needs further investigation. At the moment, there are no epidemiological data that would indicate an increase in the severity of the disease. The impact of observed immune changes on vaccine avoidance remains to be determined. Based on currently available knowledge, vaccine protection (both index and recently introduced bivalent vaccines) against infection may be reduced, but no major impact on protection against severe disease is anticipated.

Full summary

The Omicron variant of concern remains the dominant variant circulating globally, with almost all sequences reported to GISAID[1]. While we observe the vast genetic diversity of Omicron subtypes, they currently show similar clinical outcomes, but with differences in immune escape potential.

The potential impact of these variants is strongly influenced by the regional immunological landscape. While re-infections are becoming an increasing proportion of all infections, this is primarily seen against the background of primary infections unrelated to Omicron. With the weakening of the immune response from the initial waves of Omicron infection and the further evolution of Omicron variants, it is likely that re-infections will further increase.

The role of TAG-VE is to alert WHO if a variant with a significantly different phenotype (eg, a variant that may cause more severe disease or lead to large epidemic waves causing an increased burden on the health system) appears and is likely to pose a significant threat. Based on currently available evidence, TAG-VE does not consider the overall phenotype of XBB* and BQ.1* to be sufficiently different from each other, or from other Omicron strains with additional immune evasion mutations, in terms of the required public health response, to warrant justified the designation of a new variant of concern and the assignment of a new designation, but the situation will be regularly reassessed. We note that these two sublines are still part of Omicron, which is a worrisome variant with a very high potential for reinfection and vaccination breakthrough, and waves of new infections should be handled accordingly.