Abstract
In the final weeks of November, 2021, the world was introduced to the newest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron. One week later, this latest variant of concern (VOC) has already been detected in many countries around the world. Although originally thought to be receiving more attention than it deserved, it is clear now that this variant is one to watch. Omicron has received a lot of attention very quickly in part because it contains more mutations within the spike protein than any previously identified variant, and most importantly, it has mutations in common with all four previous VOCs.
The three questions we need to ask and answer when any new SARS-CoV-2 variant emerges are (1) is it more pathogenic, (2) is it more transmissible, and (3) does it affect vaccine effectiveness? The truth is, we do not know the answer to any of these questions yet, but we will know the answer to all of them within the next 2 or 3 weeks.
Will Omicron cause more severe disease in unvaccinated and vaccinated individuals? We do not know yet, but based on what we observed with Alpha and Delta variants, we have to assume that it could be more pathogenic than previous VOCs, especially if we consider the fact that it also has mutations that are known to affect antibody binding. Having said that, we are all hoping that if this virus is not going away, it will evolve to an attenuated version of itself to coexist with our species.
Until now, all of the VOCs have displayed one of two “superpowers” that were bestowed to them by the mutations they acquired—they were either more transmissible or they were less recognizable by antibodies directed against spike. The Alpha variant was deemed to be a “faster spreader,” so it dominated in many places around the world. Beta and Gamma variants both contained mutations that impacted vaccine effectiveness somewhat, but fortunately, not completely.
What is interesting is that variants with the “antibody escape” superpower were not able to dominate over Alpha. So a pattern began to emerge in which faster spreaders seem to dominate over antibody escapers. Delta variant, being an even faster spreader than Alpha variant, may have confirmed this theory because it outcompeted all other variants in most parts of the world and even began to sprout its out smaller evolutionary branches.
One major question now is, will Omicron displace Delta variant? With the mutations Omicron has in common with Alpha and Delta variants, it would not be surprising to see it spread faster than Delta variant. The fact that we are seeing Omicron at all has to be taken as an indicator that it has some kind of selective advantage over Delta variant. The epidemiology will provide the answer in the weeks to come.
The greatest concern with Omicron is whether the repertoire of mutations it has up its sleeve will impact vaccine effectiveness as well as allow it to transmit faster. Regarding vaccine effectiveness, we know Omicron also has some of the same antibody escape mutations that Beta and Gamma variants possessed. These mutations were thought to decrease the effectiveness of the vaccines against those variants, and therefore, diminished rates of vaccine effectiveness against Omicron are a real possibility.
Based on what can be inferred from the activity of the handful of VOCs we have seen to date, it appears that the variants that dominate globally are those that spread the fastest. This seems intuitive, of course, but to be more precise, the fast spreaders (Alpha and Delta) dominated over the antibody escape mutants (Beta and Gamma). If this pattern holds true, it presents three possible scenarios for the future of the Omicron variant. In the best case scenario, Omicron might have the ability to dominate over Delta variant, but the fact that we are seeing Omicron at all means that it must be a fast spreader, otherwise we would not be seeing it in numerous parts of the world already.
In another potential scenario, Omicron could turn out to be equally or more transmissible than the Delta variant. A new faster variant, with no impact on vaccine effectiveness, would mean higher risk of exposure and higher number of breakthrough infections simply due to increased opportunity for exposure, but in parts of the world where vaccines have been widely available, most people would not have to worry about getting severely ill if infected.
The real concern would be the third scenario, which, based on the mutation list associated with Omicron, appears to be a realistic possibility. In this scenario, Omicron proves to be a faster spreader than Delta, or at least fast enough to coexist with Delta, but it also demonstrates antibody escape due to the mutations it has in common with Beta and Gamma. However, even in this third scenario, we can be optimistic because the antibody escape mutations associated with the Beta and Gamma variants still only decreased vaccine effectiveness to at minimum ∼60%, which is still significant and effective coverage. From the viral immunology perspective, it will be interesting now to see whether the pivot to generating variant-specific vaccines will be as rapid as has been predicted for some of the platforms currently in use.
As unfortunate as it is that we now have a brand new VOC to get to know and understand, the emergence of this variant from wherever it originated has highlighted more than ever that we have serious vaccine inequity around the globe. Perhaps now countries that have been able to acquire vaccine stocks will be more motivated to share these stocks to prevent the emergence and transmission of additional variants.