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’
- 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
- 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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