#17,080
With Omicron subvariants BQ.1 and BQ.1.1 appearing destined - at least in the near term - to become the dominant COVID threat in Europe and the United States (see ECDC Epidemiological Update), researchers are understandably scrambling to determine what surprises this next wave may have in store for us.
Since the emergence of Omicron nearly a year ago, we've seen a rapid succession of generally `milder', but increasingly more transmissible, variants.
This much-welcomed attenuation in pathogenicity has been attributed to a reduced affinity for infecting the lower respiratory system, resulting in fewer severe pneumonia cases. A lucky break for humanity, but there are no guarantees that all future variants will retain this reduced virulence.
Attempting to peer into the not-so-distant future, we've a preprint today from researchers at Ohio State University that examines the antibody escape properties of a bevy of emerging variants (including BQ.1 and BQ.1.1), along with mutations that may help, or hinder, their replication in the lungs.
Their results - which they call `concerning' - are presented in the following 30-page preprint. They describe BQ.1 and BQ.1.1 as having both increased neutralization resistance and enhanced fusogenicity due to a key N460K mutation.
Exactly how this will translate to the real-world remains to be seen. While we are seeing rapid growth in these variants, so far we haven't seen any credible reports of increased severity. But it is still early days, and ICU admissions and deaths are generally lagging indicators.
The abstract, and some excerpts from the Discussion follow. After which I'll have a bit more.
Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2Panke Qu, John P. Evans, Julia Faraone, Yi-Min Zheng, Claire Carlin, Mirela Anghelina, Patrick Stevens, Soledad Fernandez, Daniel Jones, Gerard Lozanski, Ashish Panchal, Linda J. Saif, Eugene M. Oltz, Kai Xu, Richard J. Gumina, Shan-Lu Liu
doi: https://doi.org/10.1101/2022.10.19.512891
This article is a preprint and has not been certified by peer review [what does this mean?].
000010974
Abstract
Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ. 1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants, as well as their ancestral BA.4/5, BA.2.75 and D614G variants, against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients.We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation, and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the N460K mutation.Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity andS processing, resulting in minimal overall change.Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants.
(SNIP)
The neutralization resistance of the BQ.1, BQ.1.1, and BA.2.75.2 variants has concerning implications for the persistence of vaccine- and infection-induced immunity. The strong resistance of these variants to neutralization by patient sera, regardless of the immunogen — mRNA vaccination, BA.1 infection, or BA.4/5 infection — is particularly striking.
This finding may indicate selection for immune evasion of even broadly neutralizing antibodies induced by multiple vaccinations and SARS-CoV-2 infections, as is now common in the population. In particular, the strong evasion of BA.4/5 infection-induced sera is concerning, as the recently recommended bivalent mRNA vaccine boosters contain BA.4/5 S along with the prototype.
(SNIP)
The perpetual emergence of SARS-CoV-2 variants with enhanced immune escape continues to threaten public health. Monitoring the immune escape of emerging variants will be critical to improving mRNA vaccine reformulation, assessing new broader coronavirus vaccine candidates, as well as directing ongoing public health measures. Further, emerging variants must be monitored closely for any indication of selective pressure in enhancing lung tropism and potentially pathogenicity to ensure that any highly transmissible and more pathogenic variants are better and more quickly contained.
Although we are nearly 3 years into the COVID pandemic, the evolution and growing diversity of the SARS-CoV-2 virus continues to impress. While its future course and impact are unpredictable - in the short term, at least - we should be preparing for a challenging fall and winter ahead.
