Why viruses mutate and why they are not our enemy
And why we should be concerned, yet not panic, about the omicron variant
The news out of South Africa is concerning, as well as the recent reports that this variant may have already spread to other countries. But let’s put this whole thing into perspective, shall we?
If you have been following my writing you will be well aware that stress and panic are not good states to be in for our immune system to be functioning optimally, especially during a pandemic. So let’s all take a deep breath, calm down and learn some immunology.
At the time of me writing this, there have been less than 300 confirmed cases worldwide, 99% of them in South Africa. This number is small compared to the 600 000 cases we detect worldwide per day. It equals roughly about 0.01%.
What do we mean by confirmed?
Well, quick PCR tests reveal whether or not there has been a general mutation in the virus’ receptor binding domain (see below for more detail) - the spike protein, whole genome sequencing tells us if this mutation is of significance. And this type of genetic sequencing and analysis can take anywhere between 24-48 hours. To be able to determine whether or not this viral variant will be able to evade our primed immune response (from the vaccine) will take anywhere between 14 days to 3 weeks.
Every virologist I have read shows slight concern but they also realise that nothing has been proven yet, not the changes in symptom modality nor the mutations.
EVERYTHING is speculation at the moment and the public health authorities are erring on the side of caution.
The scientists who are working on this pandemic have a relative understanding of this, the media and the public do not. As such it is the duty of scientists and public health officials to calm rather than panic the public. It is a little bit irresponsible how this news has spread around the world like wildfire, to an already primed and anxious collective nervous system.
What did Franklin Delano Roosevelt say again:
All we have to fear, is fear itself
Viruses want to survive
Let’s roll all of this back a little bit.
Viruses want to live. Like all life on Earth, that is their prerogative. They need us to live, for them to live. It is not in a virus's best interest to kill its host. If it kills its host, it kills its means to replicate and survive. Not a very good evolutionary strategy.
Some of the most successful viruses on the planet have found a way to evade the immune system and live in their hosts indefinitely, an example of this in humans is the herpes family of viruses.
Through sophisticated techniques of inhibiting certain immune triggers, herpes has managed to live within our system as though it were one of our own cells, only replicating and “flaring” up occasionally, especially when our whole system is stressed and our immune system acts out of synch as a result.
Mutations aren’t meant to happen, and covid is slow
Mutations are mistakes and don't happen as frequently in covid as other viruses.
Covid has a proofreading mechanism most other viruses don’t possess. It mutates at a rate four times slower than influenza. It is a single stranded RNA virus, whereas influenza has 4 strands.
Again, this is the way DNA is transcribed into an enzyme:
DNA → RNA → AMINO ACIDS → PEPTIDE → PROTEIN → ENZYME
There are 29 881 RNA nucleotide bases that encode 9860 amino acids, which in turn encode a variety of peptides. The receptor domain known as “S” (or “spike”) is 1273 amino acid sequences in length. It is this S receptor-binding domain that binds to angiotensin-converting enzyme 2 (ACE-2,) expressed on human cells. So far there have been 32 “suspected” mutations (again not all of them have been confirmed as statistically significant in all cases of the partially confirmed “omicron” sightings.)
There is a fine line between mutation and viability, as in, the virus still functioning properly - most mutations result in the virus not getting assembled properly and dying (vast majority in fact.)
In the case of omicron, out of 29 881 base pairs, 32 base pairs have switched and resulted in a newly mutated variant that can replicate and still survive. In the grand scheme of things, that is not a whole lot - 0.001% of the entire virus.
By no means does this mean that the existing vaccine coverage conferred to our immune system will not work and that this mutated version will evade our already primed immune response. In fact, our immune system is so sophisticated that it can often create new binding domains if the variations of what is presented to them is not too different to the original.
Here it is important to understand the difference between two basic concepts in evolutionary biology.
Difference between antigenic drift and antigenic shift
Antigen is a fancy term used to define the part of a foreign body like a virus or bacteria that our immune system binds to.
Remember that we have B and T cells. B cells produce antibodies that bind to the viral receptor on the surface of our cells that are hosting the virus, and these bound antibodies in turn attract phagocytic (cell eating) cells to come and denature the cells harbouring the virus.
T cells are further divided into helper t cells and killer t cells. The former act very much like antibodies in mediating our immune response and communicating to other cells to come and battle the infection and killer t cells do exactly as their name suggests, they are primed to kill infected cells directly.
All three of these immune mediating pathways require receptors on the surfaces of B and T cells to recognise certain peptide subdomains in the viral receptors, this means amino acid sequences that don’t normally exist in the human body. And just like covid can mutate and shift these receptor binding sites, our immune cells can reconfigure their binding sites, especially if these don’t vary too much to the original, as with this omicron mutation.
As we just mentioned, mutations occur randomly and can accumulate over time. The evolutionary pressure for mutations is great but the need for the virus to retain some genetic familiarity is just as great, so that it can keep on replicating and surviving. Just as with the herpes virus, which mutates even slower than covid and doesn’t replicate too much so as to not burden its host too much. Again, viruses want their hosts to survive.
And this is where the importance of antigenic drift and shift comes in.
Drift is when a series of mutations are accumulated in a single species of the virus and this in turn results in a new viral variant. This is the most common form of viral mutation.
Shift occurs when several genetically distinct species of the virus (or other viruses present in the same cells as covid) mix their genetic information in one host cell and this results in a very different variant. The latter happens a lot less frequently because the likelihood of several species of virus to be in the same host cell at the same is highly unlikely (yet exacerbated in unvaccinated cohorts as the virus is allowed to multiply for longer due to the immune system being unprimed.)
An example of antigenic shift would be when covid would inhabit the same cell as a rhino virus (the virus responsible for the common cold) for instance - this could lead to a new strain that shares genetic similarity with both viruses and thus could potentially be more infectious due to enhanced immune evasion potential.
Vaccinations can prevent future omicrons - let’s share them around
Let us not forget, omicron appeared in South Africa where 24.1% of the population is fully vaccinated, and there were not many people presenting to hospitals with infections. It was precisely these conditions that allowed covid to spread silently and build up these mutations.
The other slightly depressing fact is that South Africans are eager to get vaccinated, they just can’t afford the roll out nor the cost of such a major logistical undertaking. It is time some of the richer nations got together and started sharing the vaccines they have in bulk for their own populations.
Because even if omicron is not the major threat that many public health authorities are labeling it out to be, you can rest assured that the next mutation will come from another poor nation, most probably from the African sub-continent (where the majority of countries are less immunised than South Africa,) not a suburb like Beverly Hills or Kensington.
It is also worth mentioning that it was one general practitioner in Pretoria, who noted differing symptoms in some of her patients, that led to the sequencing and subsequent discovery of this variant. It must be stressed here that none of the reported symptoms observed have been corroborated nor statistically validated - it is largely speculation at best.
Nonetheless, we must extend huge thanks and admiration to this doctor as well as to the vigilance of the local health authorities in South Africa who are acting amicably and monitoring the situation carefully.
A concerted global effort for vaccination will help eradicate this virus.
Like small pox and polio, we can get rid of covid, if we work and share together a one world. We can still do this.
One may also add here that the whole anti-vaccination sentiment is wholly a rich world phenomenon, one that is not present in poorer countries where the population seemingly recognise the gravitas of the situation as they are witnessing it with their own eyes.
And again, as for freaking out about the omicron variant, just remember it is simply way too early to tell what the impact and meaning of these mutations are. Let’s sit back, be responsible, wash our hands, practice social distancing, mask up and encourage everyone to get vaccinated.
Time will tell. Until then, let’s all keep our wits about us.
[Please let me know in the comments what parts of this article you would like explained in more detail or what may have not made sense to you]
REFERENCES
Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19
https://www.nature.com/articles/s41401-020-0485-4
Cell entry mechanisms of coronaviruses
https://pubmed.ncbi.nlm.nih.gov/20218330
Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides
https://www.pnas.org/content/101/22/8455
Coronavirus spike proteins in viral entry and pathogenesis https://pubmed.ncbi.nlm.nih.gov/11162792/?dopt=Abstract
Cell entry mechanism of coronaviruses: implication in their pathogenesis https://pubmed.ncbi.nlm.nih.gov/17446665/
Substitutions of conserved amino acids in the receptor-binding domain of the spike glycoprotein affect utilization of murine CEACAM1a by the murine coronavirus MHV-A59
https://pubmed.ncbi.nlm.nih.gov/15749126/
Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2
https://pubmed.ncbi.nlm.nih.gov/34676096
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