Don’t panic, I’m not about to get all birds and bees and storks on you, this is a microbiology blog after all… the picture is from “Sweet-Tooth” a great Netflix series where mutants are thought to be spreading a virus… timely huh?! Instead, we’re going to talk about where variants of SARS CoV2 might be arising and why they seem to pop up out of nowhere?
Look at this diagram:
Look at this diagram:
Click for larger image
This diagram is from an amazing website called Nextstrain which catalogues new sequences of microorganisms, in this case SARS CoV2. Whoa! That’s a lot of “graphed data” but what does it show? Other than the fact the scientists got an “etch a sketch” for Christmas! OK, so these diagrams are the way scientists show the relationship between variants of a virus… you’ll just have to accept that.…
In December 2020 we started to see a particular variant of SARS CoV2 which became the dominant variant, we called it Alpha. Shortly after this a new variant came along and whilst Alpha (purple-blue) continued, it was well and truly overwhelmed by the new variant, which we called Delta (turquoise). Finally, a new variant came along at the end of November 2021 and started to take over from Delta, we’ve called this Omicron (red).
This diagram “clearly” shows new variants of SARS CoV2 cropping up all the time, most of the time the new variants don’t dominate (note the greens, yellows and oranges… but don’t worry too much about the greys as these are sporadic variants that didn’t start to spread more widely!), and new variants come along to replace them rapidly. Just occasionally a new variant does start to dominate, and everyone gets excited, well Politicians do, the rest of us are getting BORED with new variants!
Are these new variants similar to the old variants? How much do they change each time? How do they occur?
Let’s look at another Nextstrain diagram:
In December 2020 we started to see a particular variant of SARS CoV2 which became the dominant variant, we called it Alpha. Shortly after this a new variant came along and whilst Alpha (purple-blue) continued, it was well and truly overwhelmed by the new variant, which we called Delta (turquoise). Finally, a new variant came along at the end of November 2021 and started to take over from Delta, we’ve called this Omicron (red).
This diagram “clearly” shows new variants of SARS CoV2 cropping up all the time, most of the time the new variants don’t dominate (note the greens, yellows and oranges… but don’t worry too much about the greys as these are sporadic variants that didn’t start to spread more widely!), and new variants come along to replace them rapidly. Just occasionally a new variant does start to dominate, and everyone gets excited, well Politicians do, the rest of us are getting BORED with new variants!
Are these new variants similar to the old variants? How much do they change each time? How do they occur?
Let’s look at another Nextstrain diagram:
Click for larger image
This is the same data as the original diagram, but this time it is presented to show how similar variants are. Each dot represents a virus, and the line pointing to the centre of the circle represents how similar variants are; the longer the line back to the centre without any interaction with other variants, the less similar the variants are. This type of diagram shows the named and coloured variants clustering together (red, blue, turquoise, etc.) and how different from each other they are. Let’s zoom in on the top left corner.
Click for larger image
Do you see how long the red line is back to the centre of the diagram? This tells us that Omicron is not that similar to any of the other variants, it has changed a lot. If anything it is more likely to have arisen from the Gamma variant (Royal blue) than any other, not Delta (turquoise) or Alpha (purple-blue).
So where has Omicron come from? How has it evolved?
The short and simple answer to this is “we don’t know”. But that wouldn’t make much of a blog (although the diagrams are pretty!) so let’s speculate a bit.
We do know that mutation in viruses in order to produce variants has to occur during viral replication inside other cells. Viruses do not reproduce themselves; they have to be in a host cell.
There are three most likely scenarios for how a new variant such as Omicron might have arisen:
1. Is it an immunocompromised person due to antigenic drift?
SARS CoV2 has a stable genome, its genetics change very slowly. Because of this there is usually not enough time during a healthy person’s infection for the virus to change much before the infection is over. This slow process of genetic change is called antigenic drift.
However, some people who are immunocompromised can have very long infections because they are unable to get rid of the virus which continues to reproduce for months inside their cells. Because the same virus can acquire lots of mutations during these months, the virus that is “around” at the end of the infection can be very different to the virus that originally infected the person. The virus has sufficient time to undergo enough antigenic drift; a new variant has been produced that looks very different to anything seen before. If this new variant then gets back out into the community it will be detected (if we look for it) and look very different to what had gone before. I know…if we didn’t go looking for “these things” we’d all sleep easier but… we just can’t help ourselves “got to measure and monitor it”!!
This is the scenario that most scientists think is the cause for the new variants of SARS CoV2, including Alpha, Delta and Omicron. These new strains then become the dominant (common) strains of SARS CoV2; note dominant isn’t being used as “worse, nastier or bigger” just “most common”.
2. Is it another mammal due to antigenic drift?
There is another scenario where antigenic drift could occur to a new variant of SARS CoV2, and that is if it is drifting in a different mammal from a human.
The first scenario of an immunocompromised person ignores the fact that coronaviruses can infect all sorts of mammals; let’s not forget that SARS CoV2 came from a spillover event, almost certainly from bats. But SARS CoV2 has been detected in cats, including domestic cats, tigers and lions, oh my! We also know that humans have been responsible for infecting other animals! Added to this it is known that after a short period of time in these animals the virus has spilled back into humans again. This is exactly what happened in mink in the Netherlands and Denmark back in April and June 2020.
So it is entirely plausible that some, if not all, of the “new variants” are spill backs from other mammals who we have infected with SARS CoV2. We are not sure, but animal to animal transmission and back might also be occurring!?
In this case the virus would have entered the non-human mammal, spread within the mammal population, possibly or probably undergoing antigenic drift until the virus has changed enough to be infectious again to humans and BANG a new variant emerges to dominate in humans.
OK, so there is no evidence for this “animal theory”, but is anyone looking at this? Not that I know of. And who would do the tests to look for mild or asymptomatic infections in pigs, cows, rabbits, hedgehogs or whatever animals?! Have your garden squirrels lost their sense of smell, who knows?!?
The US Department of Agriculture have a list of known cases of Covid-19 in animals but this is only those who have been tested. How many are there really? And what the heck is a binturong?? And who knew they had a “World Awareness Day” - 11 May!?!?
So where has Omicron come from? How has it evolved?
The short and simple answer to this is “we don’t know”. But that wouldn’t make much of a blog (although the diagrams are pretty!) so let’s speculate a bit.
We do know that mutation in viruses in order to produce variants has to occur during viral replication inside other cells. Viruses do not reproduce themselves; they have to be in a host cell.
There are three most likely scenarios for how a new variant such as Omicron might have arisen:
- In an immunocompromised person due to antigenic drift
- In another mammal due to antigenic drift
- In a healthy person due to antigenic shift
1. Is it an immunocompromised person due to antigenic drift?
SARS CoV2 has a stable genome, its genetics change very slowly. Because of this there is usually not enough time during a healthy person’s infection for the virus to change much before the infection is over. This slow process of genetic change is called antigenic drift.
However, some people who are immunocompromised can have very long infections because they are unable to get rid of the virus which continues to reproduce for months inside their cells. Because the same virus can acquire lots of mutations during these months, the virus that is “around” at the end of the infection can be very different to the virus that originally infected the person. The virus has sufficient time to undergo enough antigenic drift; a new variant has been produced that looks very different to anything seen before. If this new variant then gets back out into the community it will be detected (if we look for it) and look very different to what had gone before. I know…if we didn’t go looking for “these things” we’d all sleep easier but… we just can’t help ourselves “got to measure and monitor it”!!
This is the scenario that most scientists think is the cause for the new variants of SARS CoV2, including Alpha, Delta and Omicron. These new strains then become the dominant (common) strains of SARS CoV2; note dominant isn’t being used as “worse, nastier or bigger” just “most common”.
2. Is it another mammal due to antigenic drift?
There is another scenario where antigenic drift could occur to a new variant of SARS CoV2, and that is if it is drifting in a different mammal from a human.
The first scenario of an immunocompromised person ignores the fact that coronaviruses can infect all sorts of mammals; let’s not forget that SARS CoV2 came from a spillover event, almost certainly from bats. But SARS CoV2 has been detected in cats, including domestic cats, tigers and lions, oh my! We also know that humans have been responsible for infecting other animals! Added to this it is known that after a short period of time in these animals the virus has spilled back into humans again. This is exactly what happened in mink in the Netherlands and Denmark back in April and June 2020.
So it is entirely plausible that some, if not all, of the “new variants” are spill backs from other mammals who we have infected with SARS CoV2. We are not sure, but animal to animal transmission and back might also be occurring!?
In this case the virus would have entered the non-human mammal, spread within the mammal population, possibly or probably undergoing antigenic drift until the virus has changed enough to be infectious again to humans and BANG a new variant emerges to dominate in humans.
OK, so there is no evidence for this “animal theory”, but is anyone looking at this? Not that I know of. And who would do the tests to look for mild or asymptomatic infections in pigs, cows, rabbits, hedgehogs or whatever animals?! Have your garden squirrels lost their sense of smell, who knows?!?
The US Department of Agriculture have a list of known cases of Covid-19 in animals but this is only those who have been tested. How many are there really? And what the heck is a binturong?? And who knew they had a “World Awareness Day” - 11 May!?!?
Who knew what a Binturong was let alone that they can get covid! Cute aren't they...
Now, I don’t want this to seem like I’m blaming animals for new variants or suggesting control measure on animals to prevent spread. I have enough trouble trying to “herd” my 5 cats at home (or do they actually herd me… I’m not so sure?!), and there is no evidence to support this animal hypothesis; but then there’s also no evidence to rule it out either.
“Absence of evidence doesn’t mean evidence of absence”.
But I do think we need to think about it. All of the control measures Governments put in place to try and prevent the evolution of new variants would be pretty pointless if they aren’t actually arising in humans….
It’s a thought….
I’ll leave you to ponder that one whilst I go on to the third scenario.
3. Is it antigenic shift in a healthy person?
Spoiler alert, this scenario is the least likely because most infections in otherwise healthy people with SARS CoV2 are short, about 1 week. This doesn’t give much time for a single viral variant to mutate enough to produce such a different variant that it can become a new dominant strain. The fact that Omicron is so different to the other variants means it would have needed to change a lot of genetic material in a short period of time.
In order to change a lot of genetic material the virus would have to undergo a process we call “antigenic shift”, whereby two distinct viruses come together and swap genetic material to create a completely new variant. This happens a lot with Influenza Virus, but it is not something we have seen with SARS CoV2. We would also expect to see some similarity in the genetic record to indicate which viruses might have come together to produce the new variant e.g. H1N1 plus H2N5 forming Influenza Virus H1N5 (or Influenza Virus blah, blah, blah as ECIC puts it….)
Because of the short time scale, lack of evidence of antigenic shift and absence of similar viruses, this scenario is the least likely to have given rise to Omicron. It’s possible, just not probable.
So, which do I think it is?
I actually don’t know the answer to this. I hope it’s the first scenario of antigenic drift in an immunocompromised person because if it is then we could potentially do something about it. We can use protective isolation infection control measures to try and prevent these people getting infected in the first place, we can then vaccinate as many of them as possible to give a further level of protection, and we could then possibly use one of the new antivirals to try and speed up their recovery before the antigenic drift occurs… but this is easier said than done as it would take a massive international effort which sadly is just not happening.
On the other hand, I actually think it might be spill back from animals, and if this is the case it’s going to keep happening, and there is nothing we can do about it… so we might as well just start living with it… but then maybe we should be doing that anyway?
“Absence of evidence doesn’t mean evidence of absence”.
But I do think we need to think about it. All of the control measures Governments put in place to try and prevent the evolution of new variants would be pretty pointless if they aren’t actually arising in humans….
It’s a thought….
I’ll leave you to ponder that one whilst I go on to the third scenario.
3. Is it antigenic shift in a healthy person?
Spoiler alert, this scenario is the least likely because most infections in otherwise healthy people with SARS CoV2 are short, about 1 week. This doesn’t give much time for a single viral variant to mutate enough to produce such a different variant that it can become a new dominant strain. The fact that Omicron is so different to the other variants means it would have needed to change a lot of genetic material in a short period of time.
In order to change a lot of genetic material the virus would have to undergo a process we call “antigenic shift”, whereby two distinct viruses come together and swap genetic material to create a completely new variant. This happens a lot with Influenza Virus, but it is not something we have seen with SARS CoV2. We would also expect to see some similarity in the genetic record to indicate which viruses might have come together to produce the new variant e.g. H1N1 plus H2N5 forming Influenza Virus H1N5 (or Influenza Virus blah, blah, blah as ECIC puts it….)
Because of the short time scale, lack of evidence of antigenic shift and absence of similar viruses, this scenario is the least likely to have given rise to Omicron. It’s possible, just not probable.
So, which do I think it is?
I actually don’t know the answer to this. I hope it’s the first scenario of antigenic drift in an immunocompromised person because if it is then we could potentially do something about it. We can use protective isolation infection control measures to try and prevent these people getting infected in the first place, we can then vaccinate as many of them as possible to give a further level of protection, and we could then possibly use one of the new antivirals to try and speed up their recovery before the antigenic drift occurs… but this is easier said than done as it would take a massive international effort which sadly is just not happening.
On the other hand, I actually think it might be spill back from animals, and if this is the case it’s going to keep happening, and there is nothing we can do about it… so we might as well just start living with it… but then maybe we should be doing that anyway?
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