Why Do COVID-19 Mutations Still Infect People And Where Does Omicron Go From Here?

Many to this day, still do not understand the swiftness of Coronavirus mutations and how they compare to other viral infections like HIV, Influenza, or even Hepatitis C.

How COVID-19 Mutates

If we are to understand mutations and how they work, we have to start afresh. In a viral population, in order for a mutation to be established firmly, two distinct events are needed. One such example is the probability and occurrence of random events. This could either be the genome undergoing a random change, which can help, be neutral or even be harmful to the virus. The second event is dependent on the type and nature of this change. It could be a change in a critical amino acid of a particular protein or even the disruption of the structure of the Ribonucleic Acid (RNA) in question.

We have to understand first and foremost that these changes are all arbitrary and do not follow a set pattern, which makes it difficult to deal with COVID-19 variations like Omicron.

Another gospel truth is that coronaviruses do try and slow down the rate of their mutation, possessing a kind of proofreading mechanism in how their genomes will be replicated, and this does a check back operation to see if the replication process is flawless or not. If not it will correct them; this holds importance because of two things.

• Firstly, the rate of change happens to be much slower
• But secondly, the antiviral drugs we use at present against the virus are not as effective or not effective at all.

Our second consideration would be whether this change is an integral part of the mutation. If the change has to be accepted and ingrained in the virus, it has to be beneficial to the virus. This is because otherwise, the virus would become ineffective. It is all about the context in which we are viewing the immediate environment of the virus and ourselves.

When the Wuhan strain of the virus broke out, all of us were immunologically speaking totally naïve about it. Our immune systems were unable to comprehend the nature of the virus hence there was a distinct lack of antibodies that ideally could have prevented the virus to attach to our cells. For that particular spike protein, we had neither antibodies to do the job and neither an answer, medically speaking, except the development of vaccines.

When billions of infections are happening across the world on a daily basis, the random change mechanism will certainly come into play and at certain random times, something or the other will happen that will lead to a predominant change in the spike protein. The spike protein is the attachment that the virus uses to get access to our cells.

But then again, this is not always the way in which things get played out. Other factors also exist to influence the spread and deadliness of the virus.

One of these is that the virus itself will discover a fundamental change in itself that helps it to bind better to ourselves. As we now know, it binds to the ACE2 protein better and faster. One theory says that the virus is efficiently cut into its more active form as a by-result of cellular proteases that cut the protein itself. Or, maybe, the virus is being to avoid the antibodies that are newly being formed in the body of the vaccinated person as a result of vaccine and/or infections.

We have to also remember that any new variant is playing a numbers game. If the new virus spreads, you will definitely see more new infections due to it in your environment, as the new virus starts to outcompete, for lack of a better word, other viruses in the classic Darwin theory which says that only the fittest survive. Competition among similar viruses is hot and it is just nature’s work to filter out the less effective viruses in favor of a stronger and more virulent form.

This change takes quite a bit of time to become rampant. The variants of the virus that cause concern are from different and distinct lineages of the same mother virus, and the variations take some time to evolve. Compared to the original COVID-19 virus we saw two years ago, the viruses have stemmed into distinct lines and have been evolving all the time. One such evolution gave birth to the Omicron variant. This Omicron variant is believed to have undergone several dozen changes in its lifetime in order to be more functional, bypass vaccines and are set on different random paths where if something beneficial to the virus happens, it gets handed down to its successors in different branches.

As an example, the Alpha and Delta variants had evolved in a manner that made them highly transmissible. The binding interaction with the ACE2 protein was amplified. It also improved the processing speed and efficiency of the spike protein. Resultantly, the Alpha variant increased rates of transmission while the Delta variant had properties that could evade natural and man-made antibodies.

Omicron's Evolution

Omicron and its variants like Beta and Gamma variants were first found in South Africa and South America and these were successful in avoiding changes caused by antibodies. Again, there were other genomic changes in the virus, but what is of concern and the root of this discussion is the spike protein that dictates if or if not the transmission happens. All the vaccines being developed in the world are also targeting this spike protein angle.

Taking Omicron as an example, it has managed to accumulate multiple mutations over time, the reason being that it has branched out at a different trajectory compared to other strains of the virus. For this to happen, the virus needs the proper environmental conditions and suitable time to mutate, both of which were there for Omicron.

Based on theory what we can tell is that Omicron infected a small number of people or even a group of persons whose immunity is not strong enough. One example is the prevalence of HIV in Saharan Africa which could have led to Omicron being easily transmissible and even more deadly.

Resultantly, we find Omicron out there, trying out different permutations and combinations as time passes. Probably it was a change in a person who had a weak immune system where Omicron may have struck but the loss was contained within that person. Again, this is theory speaking. As the virus mutated, it tried out different change combinations which gave rise to the Omicron variant.

Speaking from the virus’s perspective, Omicron is a very big success. Not only is it highly contagious, but it is also fast-acting and has the capability of replication and transmission between people. Omicron spreads within the person much faster, and our immune systems cannot latch on to it in time. One small advantage of this is the fact that Omicron affects the upper respiratory tract in place of the lower respiratory tract. However most of the viruses that are respiratory in nature will begin by affecting the upper respiratory tract and then move down, so there is cause for caution.

Flu strains that are highly pathogenic like the H5N1 bird virus start their journey in the body from low down. However, endemic influenza has shifted its site of action higher up on a consistent basis. This is because of the presence of a surface protein called haemagglutinin. And, remember that the Omicron virus is in a constant state of mutation and its symptoms and mode of action could well differ as the days go by.



Omicron Sub-lineages

Omicron does not have a single lineage. Presently, scientists are well aware of three viruses that have descended from Omicron. The first, BA1 made a clean sweep of the earth in the days and weeks leading up to Christmas. BA3 was a relatively harmless variant that did not do much damage and quickly disappeared, with the exception of South Africa where it still rages in minuscule numbers.  Finally, we have the BA2 strain which has a bit of commonness with BA1. But BA2 does not fully resemble BA1 if we consider the changes that it went through to become a distinct strain.

Theories say that BA2 split from BA1 some months ago and traveled out of South Africa. It has distinct changes in different parts of the spike protein and has quite a few mutations to its credit. We are quite in the dark about the effects of BA2, but one thing is clear: BA2 has a greater transmission ability compared to BA1 which is a cause of worry. Also, BA2 is causing reinfections in large numbers of people who had been previously infected by BA1.

What we do know is that if you have taken a recent vaccination, the odds of being hospitalized with BA1 are close to nil. However, we have to wait and watch to find out the effects and the impacts that BA2 will have on the world populace. What we can take away from this information is that SARS-CoV-2 still has a long way to go before it becomes stable. You can say that it is in the works, with various tweaks and mutations. Because of its changing nature, we are far from developing immunity to it. Also, the viral evolution is sadly still going on and we cannot afford to be complacent with it.

You cannot just say that you’ve been vaccinated and will go about your daily life when Omicron is concerned. It will be a “grave” mistake as can be seen in the UK where there have been increases in infection rates among the above 55 population.

This essentially implies that Omicron, despite peaking, infections are rising in different demographics, and on the other hand, decreasing in other parts of the UK. Reports continue to pour in about the high spate of infections and increasing numbers of people being hospitalized who had previously been vulnerable to Omicron. Even as the caseload decreases in the U.S., the daily death toll remains at 1000, which is a cause of great concern. That still means well over 300,000 deaths per year. In comparison to 12,000 to 52,000 deaths for Influenza.

If you think that this virus is mild, you are making a colossal mistake. This is because the impact, clinically speaking, of the virus is determined by keeping in mind a whole host of different factors. The likelihood of a person getting infected is going to be measured (as far as possible) by their vaccination status, age, prior immunity, resilience, and many other factors.

While the SARS-CoV-2 variant, the ancestor of all these strains, had a high clinical impact, it is not the case with Omicron. However, we are just considering a 50% reduction while the Omicron virus affects a lot more people. Numbers matter.

Experts are seeing great clinical impact for those people without sufficient protection from Omicron. Recently we witnessed the bad wave in the United States, Denmark, Israel, and the UK with BA.1. We have to wait and watch, without letting our guard down.



BA 2.2 Mutation in Hong Kong

In Hong Kong, there is a BA.2 mutation in the I1221T Spike protein that is responsible for 100% cases in Hong Kong. This BA.2 sequences have a 35% growth advantage as first reported by Professor Raj Rajnarayanan. With Hong Kong, we still have two anomalies to look into. Firstly, there are still little known effects of the I1221T change on the spike protein of the body, but its effects can be seen in high hospitalization and death counts.

We should also remember that Hong Kong does not have a great record with vaccines among the older population, and it can snowball into a whole new issue. Another factor is the dearth of adopting mRNA among senior citizens. We all know that Sinovac will give you lesser protection compared to mRNA vaccines for the Omicron strain.

If we return to the subject of individual mutation, we have to remember these mutations are always viewed in the context of the many other changes that take place. Unless there is widespread infection (we hope not) we can only revert to educated guesses. Without experiments from infectious cultures, you will not get the full picture.

B.A 2.2 mutation could be linked as the reason for Hong Kong's highest death rate in the world, but we sadly know very little about the intricacies of BA 2 as of yet. We need to know the path of entry, efficiency of the spike cleavage, and other important facts before we can battle it out in the streets.  If you have not had a recent vaccination, you may struggle with your antibody defenses against the BA 2 strain.

Conclusion

Even if you are vaccinated, reinfection is a distinct probability, and that is the case in the UK now where those people who are clinically vulnerable are being overlooked still. Remember that the Omicron virus and its sublineages are not done with humankind yet, and our defenses should not falter. Again, do not be in a state of denial because that will solve nothing. It is impossible to tell what form this virus will take in the future, so our guard should be up at all times with COVID-appropriate behavior. There is a distinct possibility that we may see a Tau, Rho, or Omega in the future, so take this as a friendly warning, not to put you in panic mode but only in a better-informed position.