Naked Science Forum

Life Sciences => Physiology & Medicine => COVID-19 => Topic started by: evan_au on 12/01/2021 20:14:43

Title: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: evan_au on 12/01/2021 20:14:43
There has been an extensive "family tree" of SARS-COV2 RNA sequences created since the Wuhan RNA sequence was leaked provided to scientists outside China.

The common statistic quoted is that "SARS-COV2 virus incurs about 1-2 mutations per month".
- This is derived by looking at the RNA sequence in 1 patient, and counting the days back to the previously recorded ancestor of that virus
- That suggests to me that if there are average of 10 people infected over a month, we would expect to see 10-20 mutations appear throughout the 30,000 bases of this RNA genome
- However, if there are an average of 1 million people infected over a month, there would be 1-2 million mutations appearing. Since the genome is only 30,000 bases long, some of these mutations would make the same change to the same base, so they would be indistinguishable

If there are more mutations, it seems to me that there is an increased chance that one of these mutations (or a combination of them) would make the virus more transmissible, or change it in ways that evade the immune system or the vaccine.

Is this a reasonable scenario?
- Does having more infected people mean that there will be more total mutations in a given month?
- Does allowing the virus to roam freely increase the chance that mutations will create a new strain that needs a different vaccine?
- Have the governments in multiple countries just destroyed the effectiveness of the vaccines of which they were so proud?
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: alancalverd on 12/01/2021 23:02:49
The answer is pretty obviously yes to all three questions.

Whilst the infection rate remains below, say 20%, most of the people who receive an inoculum will not have encountered the virus previously, so it won't be competing for its preferred environmental niche or meet a prepared immune system, and can therefore multiply happily until the immune system responds. Thus any and all mutations have an equal chance of surviving the prototype stage, but those with the most cunning (i.e. not producing early symptoms or killing their host too quickly) will move on most effectively to the next stage of dispersal, and of that cohort, those with the greatest infectivity (i.e. requiring the smallest incoulum to infect a new host successfully) will spread most rapidly.

Introducing a vaccine when there is a wide range of variants but fewer infections than required for herd immunity, applies a Darwinian filter that may ensure the success  of one or more variants that are not susceptible to the vaccine-triggered antibody response.

Early and effective quarantine would have minimised the number of evolutionary routes available to the virus and thus maximised the future success of a vaccine developed to prevent its ancestors. It is quite likely now that we will have to wait until one strain dominates, and develop a new vaccine to suit it.
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: set fair on 13/01/2021 00:11:21
- Does allowing the virus to roam freely increase the chance that mutations will create a new strain that needs a different vaccine?


The harder we make it for the virus to spread, the greater the evolutionary pressure in favour a more transmissable variant.

Immunity, whether following infection or vaccination, would favour a mutation which escapes immunity. This rarely happens in viruses with a medium to low rate of mutation. Partial immunity would make this more likely, although I don't know of anyone raising the alarm when they were talking about 50% immumity from vaccines.

ps looks like it may mutate to evade immunity - see next post but one.
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: alancalverd on 13/01/2021 10:34:27
The harder we make it for the virus to spread, the greater the evolutionary pressure in favour a more transmissable variant.
The logical consequence of which is to encourage everyone to get infected as soon as possible in order to minimise the number of later infections.  Either way you end up with 100% sick and 4% dead.

"Evolutionary pressure" doesn't apply if there is no predator and no competition for a limited resource. Whichever variant you inhale in sufficient quantity will infect you, so you will end up with more people infected by whatever strain requires the smallest inoculum, replicates quickest in its host, or causes the most sneezing, but all the other variants will persist until several generations of hosts have passed.
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: set fair on 15/01/2021 00:54:42
Immunity, whether following infection or vaccination, would favour a mutation which escapes immunity. This rarely happens in viruses with a medium to low rate of mutation. Partial immunity would make this more likely, although I don't know of anyone raising the alarm when they were talking about 50% immumity from vaccines.


Might have to thing again old boy. This preprint suggests that at least one of our common cold causing coronavirus does escape immunity

https://www.biorxiv.org/content/10.1101/2020.12.17.423313v1.full.pdf
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: Edwina Lee on 15/01/2021 05:25:17
There has been an extensive "family tree" of SARS-COV2 RNA sequences created since the Wuhan RNA sequence was leaked to scientists outside China.
The RNA sequence was shared to Australia. Not leaked.
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: Edwina Lee on 15/01/2021 06:23:24
- Does allowing the virus to roam freely increase the chance that mutations will create a new strain that needs a different vaccine?

The harder we make it for the virus to spread, the greater the evolutionary pressure in favour a more transmissable variant.
Can't be true. This is like saying if we seal a virus in a jar, then the virus is more likely to jump out of the jar because it adapts. Nope, the virus does not have an intention.  Rather, it is a statistical consequence that the more viruses there are, the higher chances of variants produced.

The active virus pool will consist of all the variants which are left alive.
Those that can hide in our bodies and show no symptoms but reactivated now and then will be most disturbing to us.

I am starting to accept that this will be our future.
 
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: evan_au on 15/01/2021 11:49:43
Quote from: Edwina Lee
The RNA sequence was shared
The early days of the SARS-COV2 virus are a bit hazy.
- Hopefully, the WHO delegation which arrived in China this week can uncover some details of this pandemic origin, with an eye to avoiding future pandemics (or at least, providing a more coordinated response to them).

Reportedly, opthalmologist Li Wenliang described a cluster of SARS-like cases in Wuhan and warned other doctors on December 30, 2019.
- It then reached public attention in China
- He was arrested for spreading false rumors (or similar), and issued a retraction
- Later, he caught the virus, and died from it on February 7, 2020.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30382-2/fulltext

Meanwhile, various labs in China had obtained samples of the virus, and RNA sequences.
- There are rumors that in an initial effort to declare "everything is normal, nothing to see here", samples and records were confiscated.
- China did provide an RNA sequence to WHO on 12 Jan 2020, so "leaked" was a bad choice of words.
https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/

By the time builders started standing up a couple of 1,000-bed hospitals in Wuhan around the middle of January 2020, it was obvious that something pretty serious was happening there.

See: https://www.who.int/news/item/27-04-2020-who-timeline---covid-19
Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: Petrochemicals on 26/01/2021 18:53:34
Mathematically you would have to say yes.

Children seem to deal with the virus very quickly, with duration being like any other cold, asymptomatic cases I should think also similar to regular colds. They may be able to spread it to family, thus infecting everyone in the work school bubbles but it is dealt with very quickly. This may or may not lead to a Darwinesc ntural selection of quickly transmitted variants, but for the mutation to occur in the first place mathmatically you would need a reservoir of virus. Mathematically a person that fails to fight the virus off for a long period has a greater viral load for a much longer period. More people more virus more time can only increase the chance.

The places that mutations have occoured, South Africa, London,  Brazil and now California are all places with an ethnic mixing pot population, unlike italy or Nigeria  . They are also international centres of the Continents they are in.

Title: Re: Does a high prevalence of virus in the community lead to a higher mutation rate?
Post by: Edwina Lee on 28/01/2021 08:27:59
The smaller the infected population is, the less chance we will get a nastier mutation.
Who knows how much nastier this can get?
Can we eliminate the virus? I still hold out hope.