Variations on a theme

In music, variations are commonly used to create new musical pieces – a set of notes are played and then repeated with changes in them. Variations are used at all scales of composition and in many forms of music. The changes to the original piece of music may involve variations in melody, rhythm or harmony. The writer of variations may have created the original piece of music, or be varying someone else’s musical theme. In western classical music, there are many famous composers and musical variation compositions, including those of Bach (I remember well trying to learn his challenging unaccompanied cello variations) and Mozart. The fundament of jazz improvisation is variation.

A strong rationale for variation in music is that humans like repetition. We like to have some idea of what is coming next, rather than be completely at sea in the narrative. Repetition in musical narrative is satisfying, we recognise the series of notes, but are not bored by them being identical. We like an element of surprise – we can be pleasantly excited by how a variation changes and builds on the original.

On the variation theme, we are not so pleasantly excited by the appearance of variations in COVID-19. Variations in a virus are a normal part of its evolution, a process which affects all living organisms, and non-living organisms in the case of viruses. Viruses are not considered to be a living organism because they are not capable of reproduction on their own, they have to live in a host cell and take over its functions in order to replicate. Viruses develop variants because, when they create copies of themselves in cells, sometimes there are mistakes in the copying process, creating a mutation. Such mutations arise constantly; most have little to no impact on the virus’s ability to cause infection or the outcomes of an infection. However, some mutations do affect a virus’s properties, such as transmission (the ease with which a virus can enter cells), its ability to evade the human immune system, or severity of the illness that it causes.

The more viruses that are replicating, the more mutations that will be created and the more likelihood there is for new mutation which infect more people or make them more ill. This is the reason we should be most concerned about the mass outbreaks of COVID-19 in the world from a selfish point of view, beyond the obvious need for concern for people who are becoming sick and dying all over the world. Mass outbreaks of COVID-19 in specific areas have led to new variants, referred to by the country names.

The new variants all have one thing in common – they are more transmissible i.e. a single person infects a larger number of other people. That’s the whole ‘point’ of evolution, to be a more successful organism, where success is determined by the amount of reproduction you achieve. The new COVID-19 variants are more successful in their spread. They all have changes in the spike protein, which is part of the virus’s mechanism to attach to, and thus infect, human cells. There is little evidence of the variants killing more people, but greater lethality is not a strong driver of virus evolution – if you kill your host rapidly they don’t pass you on as much (as occurs with the Ebola virus). Transmissibility is a virus’s greatest weapon, and hugely disruptive to normal life and health systems for human beings. So what variants of note have developed?

UK variant (B1.1.7) Alpha: first discovered in Kent in September 2020 and was linked to a sharp increase in cases in the UK. It is now one of the dominant strains in the UK and has spread to at least 50 other countries. It is thought to be 30-70% more contagious than the ‘original’ COVID-19 There is some evidence that the UK strain is more lethal than the original. In terms of vaccines, the Pfizer/Biontech vaccine is very effective and the Oxford/Astrazeneca one reasonably effective against this variant, but only when two doses are given (not one). Early results for Moderna suggest it is also effective against this variant. The UK variant is now mutating further, picking up additional ability to evade the immune system (a variation seen in the South African and Brazil variants).

South African variant (B1.351) Beta: first discovered in December 2020, is now the dominant strain in much of South Africa (though to be related to the rise in cases in the first third of 2021) and has spread to over 20 countries. This variant has mutations that both increase its rate of transmission and ability to evade the immune system. It could be up to 50% more transmissible than the original. There are varying results regarding how effective the Pfizer and Moderna vaccines are against this variant, however both are developing a booster vaccine specific to it. The Oxford vaccine has relatively little protection against infection by this variant but is thought to significantly reduce severe cases and deaths from this strain. Oxford is therefore working a specific booster.

Brazil variant (P.1) Gamma: first discovered January 2021 and now is the dominant strain in Brazil (thought to be related to the rise in cases this year) and has spread to at least 37 other countries. This variant has mutations that both increase its rate of transmission and ability to evade the immune system. It could be up to twice as transmissible as the original (estimates are between 1.7 to 2.4x more transmissible). Pfizer, Oxford, and Moderna vaccines are slightly less effective against this variant than the original.

Indian variant (B.1.617) Delta: first discovered December 2020. though to be linked to the huge rise in COVID cases in India in April) . This variant has mutations different from all those above, which appear to be a new way of the virus being more transmissible and evading immune response. This variant could be 50% more transmissible than the original. Two doses of Pfizer gives high, and AstraZeneca vaccine moderate protection against this variant (one does not give effective protection).

The naming of strains changed on May 31st. There was concern that naming new strains after the country where they first became prevalent could be prejudicial. Therefore the World Health Organisation made the decision to use the letters of the greek alphabet as it is has no connotations of blame of specific groups, and it is simple. If the WHO run out of letters they will figure out a new system – we all hope it doesn’t come to that!

This is a picture of variations in the RNA structure of COVID-19 variants. N501Y, P681R and L452R are related to virus transmission (being associated with spike protein), E484K is related to overcoming antibody response. The UK variant is mutating again to include the E484K mutation. It is interesting that the first three variants have similar mutations while the Indian variant is quite different. However, a newer form of the Indian variant does include an E484Q mutation, similar to the UK, South African and Brazilian mutations – you can see documenting mutations is quite complicated!

One question that came to my mind was, why has there been no ‘USA variant’. If Trump was still in power, it is likely he would be asking this with emphasis. “How can the USA, the best at so many things, only produce weak COVID-19?” The likely answer is that the USA was not sequencing coronavirus genomes at nearly the same rate as much of the rest of the world, until early 2021. The US has decentralised surveillance, so the pieces of the COVID-sequence puzzle have not been put together anywhere. This is contrast to New Zealand, where we have relatively few cases and substantial data regarding the genetics of many cases. I imagine this will be a resource mined by researchers and postgraduate students for decades to come and is a real feather in the cap for ESR, who have been doing the heavy sequencing lifting. They produce data that means health authorities can quickly identify chains of transmission, essential to stopping virus spread.

As stated above, the most important aspect of the new variants at present, is their greater transmissibility. A small increase in the R factor, or transmission rate, can result in huge increases in the number of people infected. The goal is to keep R under 1 i.e. so that one person infects only 1 other person, or fewer and the epidemic gradually dies out. Public health measures, such as mask-wearing, social distancing and working from home, reduce the R factor. Early in the COVID-19 pandemic, it was estimated that the ‘natural’ R factor of COVID-19 is between 2 and 3. However, public health measures enacted by most countries could get the R factor to under 1. However, if a new variant is 50% more transmissible (UK, South African, Indian variants), those same measures will only bring the variant down to around 1.5. If the new variant is twice as transmissible (Brazil variant), the same measures will result in an R factor of 2. In both these cases, exponential growth of the virus is continuing, with more people infected as time goes on.

There are not going to be any new, more effective public health measures pulled out of hats. The only measure that we have to scale up our defences are vaccines. That’s why vaccine roll-out is of increasing importance as time goes on and the number virus variants rise. Every mass outbreak increases the chances of a new, more infectious variant, and every new variant increases the chances of a new outbreak. And here we are at this point, where New Zealanders have just been told that our vaccine roll-out has been delayed by a number of weeks. We all held our collective breaths during the lockdown in 2020; it’s time for more collective breath holding and finger crossing through the coming months.

Published by janecshearer

I'm a self-employed life enthusiast living in Gibbston, New Zealand

One thought on “Variations on a theme

  1. Highly informative analysis – thanks once again Jane for your thoughtful blogs.

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