COVID-19 mutations and strains

Why do we get new strains of SARS-CoV-2?


Mutants

We are all mutants, which is why we look different and our bodies work in slightly different ways. The instructions for our looks and internal biochemistry are contained on molecules of DNA. Almost every cell in your body has an identical copy of all your DNA.

DNA contains four chemical ‘bases’, labelled A, C, G and T. The order of these bases contains the coded instructions for ‘you’. When cells copy themselves, all their DNA is copied but sometimes mistakes occur. These mistakes are ‘mutations’.

Certain sections of DNA contain the instructions for making proteins that your body needs. This includes things like hormones and the enzymes you need to digest food. These DNA sections are ‘genes’. A common mutation is for a base in a gene to be changed. Sometimes this makes a cell produce a protein that has a slightly different shape to the normal protein.

When a cell makes a protein, it first makes a copy of the DNA gene. The copy is on a short length of another substance, called mRNA. This copied gene is then sent to the cell’s protein manufacture department, where the mRNA instructions are read over and over again to produce many polypeptide molecules (long chains of amino acids). After a bit of processing by the cell, the polypeptides become proteins.

So, to take an example of a mutation in a human gene, the F5 gene produces factor V, which helps blood to clot. Parts of the mRNA of two versions (alleles) of the F5 gene are shown on the right. Polypeptide 1 is the normal chain of amino acids. The mutated mRNA in the other version changes one amino acid in the chain, which changes the protein’s shape and results in painful blood clots.

Another type of mutation is when part of a gene is deleted. This usually causes a big change in the protein. The CCR5 gene produces a protein that sticks out of some white blood cells. HIV locks onto this protein. One version (CCR5-delta 32) contains a deletion of 32 bases in the gene. This produces a smaller protein, which does not stick out of cells. People with this deletion are often protected from HIV infection.

The reason why COVID-19 causes a serious illness in some people but not others is partly due to mutations. Some people may have a slightly different shape of the ACE-2 protein that sticks out of cells in the respiratory system and is the protein that SARS-CoV-2 locks onto.


Mutant viruses

The SARS-CoV-2 virus contains RNA (and not DNA). When it infects one of your cells, its RNA enters the cell’s protein manufacture department. This fools the cell into making many copies of all the virus’ proteins, which are then packaged up to form new virus particles. These then burst out of the cell and infect other cells.

During the packaging process, the human cell makes multiple copies of virus’ RNA and, as with DNA copying, it sometimes makes mistakes while doing this.

Over time, many mutations occur. They act as a ‘fingerprint’ and can be used to track how the virus spreads. Viruses with the same mutations are ‘subtypes’ or strains, and come from the same place. The map shows the tracking of some strains (in different colours) near the start of the pandemic.  

The virus locks onto the ACE-2 protein on lung cells using its ‘spike’ protein, which sticks out of the virus particle. Some strains have mutations in the S gene, which then alters the spike protein’s shape. This may make it better at attaching to lung cells, allowing it to infect more easily and so spread more quickly.


Tackling the new strains

The Pfizer/BioNTech vaccine contains the mRNA instructions for the virus’ spike protein. The mRNA gets into some of your cells and makes them briefly make the virus’ spike protein. (The mRNA lasts for about a day, and your cells can’t make copies of it.) This brief production run of spike proteins is enough to get your immune system swinging into action; it starts a process in which it manufactures ‘antibodies’. These are designed to stick to the spike proteins and help to neutralise them.

The process of making the correct antibodies that stick to the spike proteins is long and complex, which is why people get ill from viral diseases before getting better again. However, after an infection, your immune system is left with a memory of the infection, and so if the same virus enters your body, it is ready with the correct antibodies almost immediately. This prevents you from getting many viral diseases more than once.

Vaccines are designed to create that immune system memory. However, for antibodies to stick to a virus’ spike protein, they need to correctly fit the shape of the protein. If the spike protein changes shape slightly, the antibodies do not attach to it so well and some of them may fall off. That means that it takes longer for the immune system to fight off the virus. If the spike protein changes significantly, it may mean that existing vaccines will not work.

So, for COVID-19 the vaccine manufacturers will produce new vaccines containing the instructions for new shapes of the spike protein. These should be available towards the end of the year, and I would expect that we’ll all need a booster jab with one of these.

The good news is that at the moment, all the current vaccines offer 100% protection against severe COVID-19 (needing hospitalisation) in the UK. They also show at least 60% effectiveness (after just one dose) in preventing all forms of the disease, including asymptotic forms, and so transmission will also be greatly reduced as time goes on.