In a recent statement published by the World Health Organization (WHO), the TAG-VE [technical advisory group on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus evolution] of WHO, who met on October 24, 2022, presented the most recent evidence on SARS-CoV-2 Omicron VOC (variant of concern) evolution, in the context of country-level immunological differences and the high immunity levels among individuals residing in different types of settings.
To date, Omicron continues to be the predominant VOC circulating worldwide, accountable for almost all SARS-CoV-2 sequences submitted to the GISAID (global initiative on sharing all influenza data) database. The continual evolution of Omicron has led to the emergence of genetically diverse Omicron subvariants with identical disease outcomes but differences in their immune-evasive properties. WHO’s TAG-VE group conducts regular meetings to continue to assess existing data on the infection severity, immune-evasiveness, and transmissibility of SARS-CoV-2 variants and their probable diagnostic and therapeutic implications.
About the statement
In the present article, WHO’s TAG-VE group presented the most recent evidence on Omicron evolution and genetic diversity. Particularly, they discussed the public health implications of the emergence of Omicron subvariants, especially XBB and BQ.1 and their subvariants (XBB* and BQ.1*, respectively).
The XBB subvariant
XBB* has emerged as a recombinant strain of Omicron BA.2.75 and Omicron BA.2.10.1 subvariants. Based on EW 40 (epidemiological week 40, between October 3 and October 9) data of SARS-CoV-2 sequences uploaded to the GISAID database, XBB* has affected 35 nations with a one percent worldwide prevalence.
Based on regional surveillance data, the prevalence has broadly increased but has not been associated consistently with increased case counts or greater COVID-19 severity. However, the risk of SARS-CoV- infection has been reportedly greater for XBB*, compared to the other Omicron subvariants, although limited to individuals with SARS-CoV-2 exposure during pre-Omicron periods.
Studies have reported greater immune-evasiveness for XBB* compared to the other Omicron subvariants; however, whether the evasiveness is adequate to drive novel waves of SARS-CoV-2 infections would be dependent on the area-wise immunological landscapes as impacted by the timing and size of previously witnessed Omicron waves and the coverage of COVID-19 vaccinations.
The BQ.1 subvariant
BQ.1, an Omicron BA.5 subvariant, possesses N460K and K444T mutations in its spike (S) protein. The BQ.1.1 subvariant comprises an additional mutation (R346T) in a prime antigenic site of its S protein. Based on EW 40 GISAID sequence data, BQ.1* has been identified in 65 nations with a six percent global prevalence.
While data on BQ.1* immune-evasiveness or infection severity is lacking, the subvariant has demonstrated a significant GA (growth advantage) compared to other Omicron subvariants in several regions, including the United States (US) and Europe, and thus, continued surveillance efforts are warranted.
Probably, the additional mutations in BQ.1* have increased the immune-evasiveness of the subvariant, which may have increased the risk of reinfections, a probability that needs to be assessed in future studies. Existing evidence has indicated that immune protection conferred by index vaccinations and bivalent anti-SARS-CoV-2 vaccinations may be lowered without any major effect on the immune protection conferred against disease severity.
To conclude, based on the statement by the TAG-VE group, the BQ.1 and XBB phenotypes are genetically diverse from other circulating Omicron subvariants and each other with enhanced immune-evasiveness in the context of necessary population health responses to warrant novel VOC designation and label assignment.
The two strains (and their sublineages) continue to be subvariants of the Omicron VOC, which continues to be a highly transmissible and immune-evasive VOC. However, the decision would be regularly reassessed, and in case any significant development warrants population health strategy changes, the WHO would promptly alert the member states and the general public.
The potential effect of the subvariants has been influenced strongly by the area-wise immunological landscapes, and SARS-CoV-2 reinfections have increased in non-Omicron prime SARS-CoV-2 infection backgrounds. With continual Omicron evolution and the waning of immunological responses from the initial Omicron wave, the rates of SARS-CoV-2 reinfections may further increase.
Epidemiological evidence stating considerably greater risks of infection by the subvariants than by other Omicron subvariants is lacking. Moreover, the aforementioned WHO statement has been based on sentinel nation data and therefore may have limited generalizability. Systematic and wide-scale laboratory-based surveillance efforts are urgently required to make globally interpretable determinations. WHO would continue close and continuous BQ.1* and XBB* monitoring and request nations to continue their vigilant efforts and report SARS-CoV-2 sequences.