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But the short history of Omicron tells us that the dominant variant changes often, with the reign of previous variants (BA.1, BA.1.1, BA.2, BA.2.12.1) often ending after only 2 to 3 months. BA.5 may outlast its predecessors, but it will likely be supplanted by a new variant in the months ahead.
Right now, the jury is still out as to what variant will rise next to dominance, but many observers are watching the BA.2.75 variant with considerable interest. With that in mind, a handful of preprints on the relative fitness of this emerging variant for your consideration this morning.
The first is an animal study out of Japan, that finds (in Syrian hamsters, at least) that BA.2.75 has a greater affinity for the lungs than either BA.5 or BA.2. This, according to the authors, suggests that BA.2.75 could have a greater impact than the last couple of Omicron variants.
The abstract, and a snippet from the Discussion section of the PDF follow, but you'll want to read the preprint in its entirety.
Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates
Ryuta Uraki, Shun Iida, Peter J. Halfmann, Seiya Yamayoshi, Yuichiro Hirata, Kiyoko Iwatsuki-Horimoto, Maki Kiso, Mutsumi Ito, Yuri Furusawa, Hiroshi Ueki, Yuko Sakai-Tagawa, Makoto Kuroda, Tadashi Maemura, Taksoo Kim, Sohtaro Mine, Noriko Kinoshita-Iwamoto, Rong Li, Yanan Liu, Deanna Larson, Shuetsu Fukushi, Shinji Watanabe, Ken Maeda, Zhongde Wang, Norio Ohmagari, James Theiler, Will Fischer, Bette Korber, Masaki Imai, Tadaki Suzuki, Yoshihiro Kawaoka
doi: https://doi.org/10.1101/2022.08.26.505450
This article is a preprint and has not been certified by peer review [what does this mean?].
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Abstract
The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown.
Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters.Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5.Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.
We note two key limitations in this study:
(1) although hamsters are one of the most widely used animals that are known to be susceptible to SARS-CoV-2, including mice and non-human primates (Chan et al., 2020; Imai et al., 2020; Sia et al., 2020), it is unclear whether the BA.2.75 variant causes more clinically severe respiratory disease than other Omicron variants in humans; and
(2) our study was performed in immunologically naïve animals; however, many people have already acquired immunity to SARS-CoV-2 through natural infection and/or vaccination.
Therefore, it remains unclear whether our data reflect the clinical outcome in patients with immunity against SARS-CoV-2. Clinical studies are needed to corroborate our findings in the hamster model.
In summary, the prevalence of BA.2.75 has increased throughout India, and has been increasing faster in regions where BA.5 and BA.2.75 are co-circulating, suggesting the potential for BA.2.75 to become the next globally dominant variant.
Our data show that, compared to BA.5 and BA.2, BA.2.75 can replicate efficiently in the lungs of hamsters and cause more severe respiratory disease. This higher replicative ability of BA.2.75 in the lower respiratory tract may affect the clinical outcome in infected humans. Accordingly, the spread of this new variant should be monitored closely.
Our next stop is also from Japan, is an analysis of the increasing evolutionary distance of the S gene of BA.4/5 and BA.2.75 from the original Wuhan strain - and their docking affinity with ACE2 - in an attempt to predict their relative infectivity.
SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variantsAki Sugano, Yutaka Takaoka, Haruyuki Kataguchi, Minoru Kumaoka, Mika Ohta, Shigemi Kimura, Masatake Araki, Yoshitomo Morinaga, Yoshihiro Yamamoto
doi: https://doi.org/10.1101/2022.08.25.505217ABSTRACT
Objectives: In our previous research, we have reported mathematical model with molecular simulation analysis to predict the infectivity of seven SARS-CoV-2 variants. In this report, we aimed to predict the relative risk of the recent new variants of SARS-CoV-2 based on our previous research.
Methods: We subjected Omicron BA.4/5 or BA.2.75 variant of SARS-CoV-2 to the analysis for the evolutionary distance of the spike protein gene (S gene) to appreciate the changes of the spike protein. We performed the molecular docking simulation analyses of the spike protein with human angiotensin-converting enzyme 2 (ACE2) to understand the docking affinity in these variants. We then compared the evolutionary distance and the docking affinity of these variants with that of the seven variants which were analyzed in our previous research.
Results: The evolutionary distance of the S gene in BA.4/5 or BA.2.75 from the Wuhan variant were longer than the other variants. The highest docking affinity of the spike protein with ACE2 (ratio per Wuhan variant) was observed in BA.2.75.
Conclusion: It is important to note that BA.2.75 has both the highest docking affinity and the longest evolutionary distance of the S gene. These results suggest that the infection of BA.2.75 can be spread further than preexisting variants.
While both of these preprints paint BA.2.75 as a potentially formidable foe, it is worth noting that we've been led astray by animal models before, and mathematical models don't always pan out in the real world.
Time will tell.
To end on a slightly less somber note we have a preprint from Sweden that suggests that BA.2.75 remains largely susceptible to bebtelovimab monoclonal antibody treatments, and is moderately susceptibility to tixagevimab and cilgavimab.
Evasion of neutralizing antibodies by Omicron sublineage BA.2.75
Daniel J. Sheward, Changil Kim, Julian Fischbach, Sandra Muschiol, Roy A. Ehling, Niklas K. Björkström, Gunilla B. Karlsson Hedestam, Sai T. Reddy, Jan Albert, Thomas P. Peacock, Ben Murrell
doi: https://doi.org/10.1101/2022.07.19.500716
Abstract
An emerging SARS-CoV-2 Omicron sublineage, BA.2.75, is increasing in frequency in India and has been detected in at least 15 countries as of 19 July 2022. Relative to BA.2, BA.2.75 carries nine additional mutations in spike. Here we report the sensitivity of the BA.2.75 spike to neutralization by a panel of clinically-relevant and pre-clinical monoclonal antibodies, as well as by serum from blood donated in Stockholm, Sweden, before and after the BA.1/BA.2 infection wave.
BA.2.75 largely maintains sensitivity to bebtelovimab, despite a slight reduction in potency, and exhibits moderate susceptibility to tixagevimab and cilgavimab. For sera sampled both before and after the BA.1/BA.2 infection wave, BA.2.75 does not show significantly greater antibody evasion than the currently-dominating BA.5.
SARS-CoV-2 remains notoriously unpredictable, and trying to guess where we will be with this pandemic 3 or 6 months from now is a fools game. BA.2.75 may never ascend to dominance, but if it does, these early preprints can provide us with some insight as to what to expect.
