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Genetic mutations in the virus and in humans: Do they offer a way out?

As the pandemic progresses the virus mutates. Mutations in us result in differences in how our immune system fights the infection. In this post I review how recent research on the impacts of these mutations could change the way we control and treat the disease – I found the results really interesting and even hopeful!

What is a mutation?

  • The different genes in every organism, from virus to man, consist of chains of different sequences of 4 building blocks, called nucleotides
  • The 4 – referred to as ‘A’, ‘C’ ‘G’ and ‘T’- can form very long sequences with up to 2 million in  any one gene 
  • You can think of genes as very long necklaces made up of Lego blocks in the 4 main colours
  • The exact sequence of the nucleotides in each individual gene does vary:
    • no two humans have identical sequences in any of our genes: there are many points of difference
    • even though a virus has far fewer and much shorter genes, there can be many differences in the genes (these are then referred to as different ‘strains’)
  • Such differences in the sequence of nucleotides are referred to as mutations. Mutations continually occur in all species
  • In some mutations, there is a substitution of one nucleotide for another
    • In the example below a  ‘red’ T was substituted by a ‘blue’ ‘C’
source: http://biology4alevel.blogspot.com/2016/06/133-genetic-mutations.html
  • In other mutations, sequences can be missing from one gene to another: this is called deletion
  • In yet other mutations, extra sequences can be added, often copies of short sequences, this is called duplication

How common are mutations in the Covid-19 virus?

  • This virus just has one strand of the genetic material RNA
  • This strand though has 30,000 nucleotides
  • Already scientists have identified 13,000 separate mutations 
  • Although this might seem very high, the level of mutations is 6 times lower than in the influenza virus 

What are the potential consequences of Covid-19 mutations?

  • Most mutations will have no consequences in terms of the infection
  • Even so, identifying such individual mutations can be very helpful in tracking the spread of infection between people
  • Of those that do make a difference, some mutations can affect the transmissibility of the virus (ie how easily it spreads) and others the severity of the infection
  • Early on in the pandemic, one mutation (OK it’s called D614G) was thought to be responsible for altering the spike protein on the surface of the virus that causes it to stick to human cells (and is the bit that most vaccines are directed against)
  • This mutation is now present in 80% of Covid-19 virus samples studied
  • The Chilean outbreak is thought to be due to further mutations in the spike protein gene making it even more sticky to human cells
  • There are other mutations, associated with a deletion of some of the virus’s genetic sequence, that make it less infectious
  • A study from Singapore in the Lancet in August suggested that that country’s lower death rate may be due to a deletion which produces less severe disease

The results were impressive-Singapore has lowest fatality rate in the world:

  • What is interesting is that mutations in the virus are likely to occur in response to how humans combat the infection.  There could be both beneficial and harmful consequences:
    • Beneficial: Consider for example there are two mutations: the one that causes very serious infections and the other that causes mild infection.  People carrying the latter are more likely to spread the infection and thus that version of the virus will become more prevalent.
    • Harmful: There are several examples of  viruses mutating to try and overcome our body’s immune response
  • We should not forget that significant (but what significant means is difficult to be precise) mutations in the virus could affect the success or otherwise of any new vaccine
  • Although at the moment most vaccine researchers believe their vaccines should be resilient against the types of mutation currently recognised  

How common are mutations in humans?

  • The answer of course is immensely common, each one of us probably has millions of mutations
  • Many of these mutations affect how our immune systems fight infections
  • The interesting question is therefore to ask if mutations in these immune genes explain why some people have more serious infections than others
  • The short answer from a vast number of research studies is yes:  differences in these genes between people are linked to various dimensions of the outcome, including mortality
  • An example of a recent study is the one referred to below from the USA that showed that some people have a mutation that reduces the body’s production of interferon, which is our natural anti-viral drug. 
  • Indeed, other studies have shown that an effective interferon response is necessary to fight this virus
  • To be honest, at first sight knowing that people who have more severe disease than others have a genetic basis for this might seem not that helpful, as we cannot change our genes
  • But what this kind of research can do is to help suggest new drug possibilities.  Just yesterday came a press release from the biotech company ILC Therapeutics for an inhaled version of interferon that might be a useful new drug
  • This follow from another small UK study in July of the use of another type of  interferon which showed an 80% reduction in the likelihood of severe complications
  • These are early days and more evidence is needed

Conclusions

  • There has been a massive amount of research into the genes that:
    • allow Covid-19 to invade and cause such mayhem
    • impact on our immune response 
  • None of the research findings individually will be a game changer, there is a very complex jigsaw of how all the pieces fit together 
  • A better understanding of the mutations in the virus can help in tracking the infection both over time and between regions and local outbreaks
  • More importantly these insights from genetic mutations can help focus attention on novel approaches to treating the infection    

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3 replies on “Genetic mutations in the virus and in humans: Do they offer a way out?”

Excellent blog Alan. You are a very good explainer, and must have been a very good teacher! Lucky medical students, juniors and PhD students!!

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Thanks for this insightful paper. It strikes me that as mutations occur naturally and may have a beneficial or detrimental or no effect on the organism there seems to be no way we can do anything about these changes.

When mutations occur in a virus do they only affect those in a particular host? How do we get the mutation which might help us to get spread through the whole virus population?

Isn’t evolution a development of organisms that have mutations that either help the organism survive or cause it to fail in the long or short term. In more complex organisms these mutatons can take thousands of years. I unerstand for insects who have a massive rate of reproduction they can go through many generations in a matter of weeks or months.Do viruses work in any way similar to that ?

I understand viruses are not always classed as “life forms” perhaps between living and non-living things but how does it work in them. I personally tend to think of them as alien invaders as they don’t fit in to animal or vegetable life forms

A mutation seen in a strain in one country that makes the virus less harmful is fine but how can that be replicated elsewhere or can it ?

With the flu virus, it seems to annually mutate into a different strain but still remains very damaging.

What do you think?

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