Cambridge: It is debatable whether viruses are alive, but like all living things, they keep evolving. This fact became abundantly clear during the pandemic as new varieties of concern emerged every few months.
Some of these variants were able to spread better from person to person and eventually became dominant as they crowd out slower versions of SARS-CoV-2, the virus that causes COVID-19.
This improved ability to spread has been attributed to mutations in the spike protein, the mushroom-shaped protrusions on the surface of the virus that allow it to bind more strongly to ACE2 receptors. ACE2 are receptors on the surface of our cells, as they line our airways, that the virus attaches to in order to gain entry and start replicating.
These mutations enabled the alpha variant and then the delta variant to become globally dominant. And scientists expect that this will also happen at omicron.
However, the virus cannot improve indefinitely. The laws of biochemistry mean that the virus will eventually develop a spike protein that will bind to ACE2 as tightly as possible. At this point, the ability of SARS-CoV-2 to spread between people is no longer limited by how well the virus can adhere to the outside of the cells. Other factors will limit the spread of the virus, such as how fast the genome can replicate, how fast the virus can enter the cell via the TMPRSS2 protein, and how much virus an infected person can shed. In principle, all of these should develop to peak performance at some point.
Has omicron reached this peak? There is no good reason to assume that this is the case. In so-called gain-of-function studies, which investigate which mutations SARS-CoV-2 needs for more efficient distribution, numerous mutations have been identified that improve the ability of the spike protein to bind to human cells that Omicron does not have . In addition, other aspects of the virus life cycle could be improved, such as genome replication as I mentioned above.
But let’s assume for a second that omicron is the variant with maximum spreadability. Maybe omicron is not getting better because it is limited by genetic probability. Just as zebras did not develop eyes on the back of their heads to avoid predators, it is plausible that SARS-CoV-2 cannot intercept the mutations required to reach a theoretical maximum, as these mutations must all occur at once, and that’s just too unlikely. Even in a scenario where Omicron is the best variant for diffusion between people, new variants will emerge to dominate the human immune system.
After infection with a virus, the immune system adapts by making antibodies that stick to the virus to neutralize it and killer T cells that destroy infected cells. Antibodies are pieces of protein that adhere to the specific molecular form of the virus, and killer T cells use the molecular form to recognize infected cells. SARS-CoV-2 can therefore evade the immune system by mutating to such an extent that its molecular form changes beyond the recognition of the immune system.
This is why omicron appears to be so successful in infecting people with prior immunity, whether through vaccines or infections with other variants. The mutations that allow the spike to bind more strongly to ACE2 also reduce the ability of antibodies to bind to the virus and neutralize it. Pfizer’s data suggest that T cells should respond similarly to Omicron as they did to previous variants, which is consistent with the observation that Omicron has a lower death rate in South Africa, where most people are immune.
It is important for humanity that past exposure still protects against serious illness and death, which leaves us a compromise where the virus can replicate and re-infect, but we don’t get as seriously ill as the first time .
Herein lies the most likely future for this virus. Even if it behaves like a professional gamer and eventually maximizes all of its stats, there is no reason to believe that it is not being controlled and eliminated by the immune system. The mutations that improve its ability to spread do not significantly increase deaths. This exhausted virus would then simply randomly mutate and change over time to such an extent that it can no longer be recognized by the adapted defenses of the immune system, which enables a renewed infection.
We could have a COVID season every winter, just like we have the flu season now. Influenza viruses can also exhibit a similar pattern of mutations over time known as antigen drift, which leads to reinfection. The new flu viruses each year are not necessarily better than last year, just sufficiently different. Perhaps the best evidence of this eventuality for SARS-CoV-2 is that 229E, a coronavirus that causes colds, is already doing so.
So Omicron won’t be the last variant, but it could be the last worrying variant. If we’re lucky and the course of this pandemic is difficult to predict, SARS-CoV-2 will likely become an endemic virus that slowly mutates over time.
The disease is very likely to be mild as previous exposure creates immunity that reduces the likelihood of hospitalization and death. Most people become infected the first time as a child, which can happen before or after a vaccination, and subsequent reinfections are barely noticed. Only a small group of scientists will track the genetic changes in SARS-CoV-2 over time, and the worrying variants will be a thing of the past at least until the next virus crosses species boundary. (The conversation)