Although the mutation rate of coronaviruses is relatively slow, there are many thousands of mutations that have occurred in the SARS-Cov-2 virus to-date; most of these are inconsequential with regards to infection and pathology. However, about 12 distinct…
clades of the virus have now emerged and the most concerning are the ones that involve mutations in the spike protein (and particularly, the receptor-binding domain).
Identification of mutations is a simple procedure involving sequencing the genome of the virus; and some countries are doing better than others at sequencing, Denmark is a great example of diligence, and has recently began to sequence the viral genome from every single positive coronavirus test.
While sequencing is quite easy, determining the biological consequences of mutations is more difficult and time consuming. Molecular modelling offers a rapid approach of getting overall picture of the potential effects of mutations on the binding of the SARS-CoV-2 virus to ACE2 receptors on host cells. However more in depth epidemiological and laboratory studies are required to get complete understanding of virulence and changes in pathological features.
Humans are fascinated with mutations and evolutionary processes. The topic is too broad to describe here and there are too many examples of real evolutionary processes, and those created by the human imagination; the ancient fire-breathing Chimera of Lycia highlights that imagining mutants is not a modern human issue. Back to reality, most people are familiar with Darwinian evolution – random mutations , selective pressure, evolutionary (reproductive) advantage, survival of the fittest etc… Viral evolution follows this type of process. Briefly, erroneous replication leads to mutations and most of these are “useless” and either diminish or have no effect on the virus’ ability to replicate. In some cases random mutations give the virus a selective advantage in terms of being able to infect cells or to replicate. These can be referred to as “fitter” viruses which then eventually become the new dominant clone.
With SARS-CoV-2 the D614G variant was one of the early mutated versions; an amino acid change (from an aspartate to a glycine at residue 614) in the spike protein gave the virus a selective advantage and became the dominant clone around the world. In terms of infectivity and pathology luckily this “mutant” did not have major consequences. More recently a new SARS-Cov-2 variant that emerged (B.1.1.7), in the UK is associated with many more mutations, including on the spike protein and is known to be at least 50% more transmissible; the version has spread quickly throughout the UK and in many other countries. While it is still uncertain whether the is version is associated with more severe pathology, the higher transmissibility means that more people will be infected, which in turn means more hospitalizations and ultimately death. [It has been suggested that this version may be more deadly by a factor of 1.3; still controversial].
Perhaps the most concerning new variant is the South African (B.1.351) variant (by the way, the “authorities” need to come up with a better, more intuitive naming system – this is getting confusing), which has sensationally been referred to as an “escape variant”! Of course, viral mutations is an important issues and has become a “trending “ story; there have been many headlines including announcing new strains such as the “Columbus strain, a new variant found in the Bay Area (SF), worrisome California variant, a new variant in a German hospital linked to an outbreak in Kaiser, and a new variant found in people who travelled from Japan to Brazil”. It appears that along with the UK and South African variants, the Brazilian P1 (and P2) coronavirus variants are of most concern at the moment.
Apart from becoming the new dominant strains (the UK variant is already on its way), the concern is that the COVID-19 vaccines, which are thankfully are now becoming increasingly more now widely available and distributed, may not be as effective against these emerging variants. [Incidentally, an 108-year-old Italian (109 on June 3), lady who was diagnosed with COVID-19 May, is probably the oldest known person to have been vaccinated against COVID-19!]. At this stage all indications are that the current vaccines will be effective against the known new SARS-CoV-2 variants; there are still some questions regarding the South African variant.
What does all this mean in the context of the COVID-19 pandemic? We are currently in race to achieve herd immunity with our current “batch” of vaccines, before an even more highly transmissible and “pathologically active” variant emerges that may re-ignite infection. Looking forward, it appears that unless totally eliminated (highly unlikely), COVID-19 will require (probably) yearly vaccination top-ups to protect from emerging variants to keep the virus under control.
Until next time … Tranquilo Polymaths.