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How and why do viruses mutate?

Biology/Immunity Vaccines

Q: What does this mean for future SARS-CoV-2 variants?

A: After infection, the virus makes lots of copies of itself in the body which can lead to random changes (like typos) in the virus’ genetic code (mutations).

While most mutations give no advantage to the virus, with enough chances for mutations, sometimes the virus hits the lottery with a change that helps it survive and reproduce better.

A new variant that is more infectious can spread rapidly and become the dominant strain (as seen with Delta). What does this mean for the future? As the human population builds up immunity through vaccination, SARS-CoV-2 will have less opportunity to replicate and generate new variants. Right now, our best option is to get the world vaccinated and give the virus fewer chances to win the mutation lottery.

➡️ TL;DR: Mutations are random changes in viral genetic code (either DNA or RNA). The majority of mutations are harmful to the virus, others are neutral, and some (the most concerning ones) can make the virus more infectious, evade the immune system, or become capable of jumping across species. As more immunity builds up across the world through vaccinations, fewer people are likely to get infected with SARS-CoV-2, thus giving the virus less opportunity to replicate and mutate.

So far the vaccines work very well against the variants, as our immune systems build multi-pronged defenses to recognize many different parts of the spike protein. While it considered unlikely that a variant could completely evade immunity, it is possible that a SARS-CoV-2 variant could emerge that evades immunity more than we are currently seeing. The pressure is on US to not give SARS-CoV-2 enough chances to get that lucky.

Contrary to some things you might have heard, vaccines do not encourage the development of variants. (See recent post here.)

❓ How do viruses replicate?

Viruses are composed of genetic code (DNA or RNA) packed inside a protein shell that might be covered by an outer envelope. Viruses lack the machinery needed to replicate and must find a host cell to do so. When they enter a host cell, they hijack the cell’s machinery and proceed to make more copies of themselves. The newly copied viral RNA or DNA is packed into a protein shell and released from the host cells, causing cellular damage along the way.

❓ How do mutations occur?

The process of virus replication is not foolproof. Each time the virus makes a copy of its DNA or RNA, there’s a chance that random errors are introduced. These errors, that are similar to typos in a sentence, are called ‘mutations’. Most mutations are harmful to the virus and prevent it from replicating. For instance, mutations in the genetic code might lead to misformed proteins that cannot assemble a protein shell around the new viral DNA or RNA.

Other mutations that change the DNA or RNA sequence do not lead to any change in viral proteins, and therefore no change to the original virus. However, some mutations give the virus a survival advantage – they may help the virus jump from one host species to another, or help the virus attach more tightly to a cellular protein thus making it more infectious, or escape the immune response to the virus. These mutations are the ones that are most concerning to us.

❓ Why do errors in the genetic code occur?

Viruses make use of an enzyme called a ‘polymerase’ to copy their genetic code. DNA viruses make use of the enzyme ‘DNA polymerase’ – DNA polymerases are able to proofread the newly copied viral DNA and go back and fix errors (like the ‘spell check’ function). DNA viruses therefore have fewer mutations when they are copied. RNA viruses use ‘RNA polymerase’ that is pretty bad at fixing errors. Therefore, RNA viruses have a much higher mutation rate – up to a million times more than DNA viruses!

❓ What does this mean specifically for SARS-CoV-2?

Coronaviruses such as SARS-CoV-2 are RNA viruses and are more prone to making mistakes when they replicate. When SARS-CoV-2 infects a person and makes millions of copies of itself, MANY different versions of its RNA are made and not all of them result in a live virus. A version of SARS-CoV-2 RNA that results in live virus, and in particular that has an advantage over the original infecting virus, can become the dominant variant in the community. This is what has happened over the course of the pandemic. The original Wuhan strain has been replaced by other variants (Alpha (UK), Beta (South Africa), Gamma (Brazil) and Delta (India) (shown in attached picture and in LINK to reference below). Delta has the advantage of being able to spread between people much faster than the other variants and is rapidly replacing them across the world.

❓ How do SARS-CoV-2 mutations impact COVID-19 vaccine efficacy?

How far a variant drifts from the original strain may tell us something about how effective the vaccine-induced immune response will be against it. An antigen map of the current variants shows that most of the current variants cluster fairly close to the original Wuhan strain (shown in the attached picture, and in LINK to reference below). This means that antibodies to one strain can neutralize another variant that is close by on the map. Delta, the dominant variant, is further away than Alpha. While vaccination does protect against the Delta variant, Delta is also more likely than Alpha to infect fully vaccinated people who can then spread it to other people. Although Beta is furthest away, current vaccines DO protect against this variant. Thus, further research is needed to fully understand the vaccine response and its effect on variants.

❓ So, what does this mean for the future of the pandemic?

How fast SARS-CoV-2 mutates depends on how many people it is able to infect and how quickly it does so. Every chance that the virus gets to replicate means an opportunity for more mutations, and potentially new variants. If a significant number of people across the globe are vaccinated, there will be fewer opportunities for SARS-CoV-2 to infect people, replicate, and experiment with new mutations. This is the best scenario. At the other end of the spectrum is the possibility that SARS-CoV-2 will develop mutations that escape the immunity we have built up through vaccination. For the virus to be effective, it has to develop mutations that help it evade the immune system, continue to be infectious, and be able to replicate to high numbers.

Scientists think that SARS-CoV-2 may be reaching its limit of transmissibility, however it is not possible to predict when and if a new variant might emerge. This is why keeping a close watch on the behavior of SARS-CoV-2 is so critical. It’s very likely that SARS-CoV-2 is here to stay. With increasing immune pressure as more people develop immunity, it may become endemic and lead to localized outbreaks of infection in people who lack sufficient immunity to the virus. The bottom line is that it is difficult to predict what course the virus will take.

❓ What can WE do at this point in time?

Our best defense against SARS-CoV-2 RIGHT NOW is to get vaccinated! The more people who develop an immune defense against the virus, the less opportunity it has to mutate. The more people vaccinated, the more protection offered to our vulnerable populations who may not make a good response to vaccines or who are not yet eligible to get vaccinated.

Stay safe! Get vaccinated!

Love,
Those Nerdy Girls

📚 Further reading:

What will the virus do next?

The coronavirus may be here to stay.

CDC on variants

Previous Dear Pandemic post on vaccines and emergence of variants

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