Is Omicron the Last One?

The whole world has become a little more familiar with the Greek alphabet over the past two years. Some would even say the pandemic is over, and in many ways, it certainly feels like it is, but every virologist and immunologist on the planet knows that any day, a new variant could emerge. When the Delta variant began to generate subvariants, it seemed like it was settling in to become the dominant and final variant from which all others would evolve. The arrival of the Omicron variant was quite unexpected, and fortunately, has proven to be the “mild” variant we all heard and hoped it would be. Although, as many of us noted very early on, it has not been mild for everyone it touched.

In many parts of the world today, one will find a complete lack of masking, and public gatherings in numbers reminiscent of pre-2020, which, thankfully, feels “normal” again. Despite that, if there is one thing this virus has taught us, it is that it can surprise us and turn the tables quite rapidly at any time. So, the biggest question right now would be, is Omicron the last Variant of Concern (VOC)?

As mentioned above, the Delta variant seemed to be behaving as if it was going to be the final dominant VOC that would generate multiple offspring, but Omicron emerged quite surprisingly, and has now displaced Delta and is now generating its own family of offspring, even chimeric versions of itself. So again, we have this feeling of relief that we know what we are dealing with, and we feel confident that the slow end to the pandemic is back on course. However, Omicron emerged because, despite the Delta variant being quite dominant, there was still some Alpha or Beta variant out there, smoldering quietly, that likely brought Omicron into existence. At this point, we know there is still some Delta variant circulating, so who is to say that we are not about to see the next Greek letter having a Delta backbone?

We hope that Omicron will be the last one, the last VOC, and the new normal will continue to present us with a mild variant that will only get milder as general immunity accumulates through the combination of continued vaccination and the unavoidable extensive natural infection we are seeing around the world. It is impossible to predict which way things will go at this point. The more the Omicron variant diversifies itself, the more it will seem to look like the new wild-type, but in that diversification there is also the risk for something different to emerge.

The generation of recombinants was always believed to be possible. Viruses do that. Viral polymerases fall off templates only to reanneal and pick up where they left off. But to generate a recombinant genome, a single-stranded virus such as a coronavirus requires that an individual be simultaneously infected with two different variants, and even then, both variants must be present in the same cell for recombination to occur. Usually sick people stay home, so they do not have the opportunity to get superinfected, i.e., infected twice simultaneously, especially with different variants or subvariants, but obviously, this has happened at least a few times already. This is not surprising at this point, given the fact that many people have such mild infections that they do not even know they are infected. Unfortunately, such individuals are also potential incubators for new variants.

Whether or not the Omicron variant will be the last VOC will also help us figure out where we need to go with vaccine development. Despite high breakthrough rates, the vaccines are clearly reducing disease severity, at least for those with competent immune systems who can appropriately respond to the vaccines. An Omicron-specific vaccine might do a better job at preventing actual infection, but if additional VOCs emerge, we will always be playing catch up with the vaccines. Hopefully Omicron is actually the last VOC, and we can focus on that one from now on.