COVID-19: Is the virus mutating? © NIAID Integrated Research Facility, Fort Detrick, Maryland

COVID-19: Is the virus mutating?

Occasionally, viruses mutate in a way that gives them an advantage in spreading through the population.

For most viruses, replication involves making many errors. This means that viruses like the flu mutate rapidly. This can mean that many treatments and vaccines become ineffective, and is one of the reasons why we need a new flu jab every year.

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However, coronaviruses proofread their replicated genome and so they accumulate mutations at a slower rate. Mutations do occur, though, and could have many different effects on the SARS-CoV-2 coronavirus and our ability to control the pandemic.

The majority of mutations will have no impact on the virus or on the disease. Occasionally a mutation will enable greater growth, transmissibility or escape from the immune system, in which case the mutated virus may spread widely throughout the population.

However, it is important to note that increased virus replication or transmission does not necessarily mean that the virus will become more deadly. For SARS-CoV-2, its ability to spread asymptomatically and pre-symptomatically has made the pandemic much more difficult to control and has greatly increased the number of infections.

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The 2002-2003 SARS-CoV-1 virus was a more lethal virus, but the outbreak was easier to control because it spread after symptoms began. Causing serious disease is not always in a virus’s ‘best interest’.

We have already seen this phenomenon occur with the much discussed D614G mutation of SARS-CoV-2, which arose in February 2020. This mutation in the viral spike protein (the spike protein is the part of the virus used to invade human cells) enabled the virus to transmit more effectively from person to person, but did not affect the disease severity.

Due to this enhanced transmission, the D614G variant became the dominant form of the virus by March 2020 and continues to be the main form of the virus seen in most infections.

The D614G mutation is not the only mutation that has been observed in SARS-CoV-2. So far, however, no other mutations have been observed that change the virus’s replication, transmission, disease or immune evasion. These mutations are still possible at any time, and the longer the pandemic continues the more likely it will be that we will see another important mutation arise.

Any mutation may change the behaviour of the virus, though when and in what way is impossible to predict.

The impact of viral mutations could change once we start using antiviral therapeutics and vaccines to combat the virus. The use of these treatments puts a selective pressure on the virus, effectively encouraging mutations that render the treatment ineffective.

For example, the antiviral drug remdesivir targets the polymerase protein that replicates the viral genome. Normally, mutations in the virus polymerase protein are disadvantageous as they can impair the function of a critical virus protein,  but if the mutation stops remdesivir from working, then the virus can continue to replicate and spread and we would have one less therapeutic to use against the virus.

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Similarly, some vaccines, such as the Oxford ChAdOx1 vaccine, generate immune responses to the viral spike protein. Mutations could alter the spike protein so that vaccine-generated antibodies would not recognise it so well, reducing vaccine effectiveness.

However, there are 316 different therapeutics and 213 different coronavirus vaccines currently in development. If we see mutations arising that alter the effectiveness of any one therapeutic or vaccine, we may then be able to vary or combine therapeutics, preventing virus escape from the treatment and ensuring effectiveness.

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Thankfully, SARS-CoV-2 mutates very slowly. Because of this, it is likely that our new treatments will continue to be effective and that the behaviour of the virus will not dramatically change over the coming months. However, it is important to work toward viral containment and ending the pandemic, because the longer the virus continues to circulate, the greater the chances of a new mutation emerging.

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