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A sign reminds arriving passengers to quarantine against COVID-19 at Trudeau Airport in Montreal, Friday, Feb. 19, 2021.Ryan Remiorz/The Canadian Press

One look at the list of mutations on the Omicron variant helps explain why scientists are reacting so differently to this iteration of SARS-CoV-2, the coronavirus that causes COVID-19.

Even before delving into the biological details of what each mutation represents, it’s the length of the list that is so striking.

When lined up side by side, the mutations of each of the previous four variants of concern – Alpha through Delta – can be thought of as different models of cars speeding down the highway. In contrast, Omicron looks more like a transport truck, with a list of changes more than three times longer.

The Omicron COVID-19 variant is sparking global concern. Here’s everything you need to know

The question on everyone’s mind now is what all those mutations may mean for the dynamics and character of COVID-19 as a disease. The number of mutations is enough to suggest that vaccines may have a harder time preventing infection by Omicron, though it is too early to know if this will mean more cases going to the hospital. So far, vaccine makers Moderna and Pfizer-BioNTech have given somewhat divergent statements on how much of a problem they perceive the variant to be. The fact is no one really knows for sure, since it’s far easier to spot a mutation than to understand what it does.

Mutations are a regularly occurring feature in any virus. They are changes to the virus’s genetic code, which, in the case of SARS-CoV-2 comprises a long strand of RNA packed into each viral particle. The code is what gets translated into proteins, molecular building blocks assembled out of amino acids, then organized to manufacture new copies of the virus. Since the virus can’t do this on its own, it has to infect and then commandeer the protein-building machinery of host cells. Each new virus made in this way is packed with a fresh copy of the RNA instruction kit and sent on its way to infect another cell.

Sometimes the daughter virus particles carry copying errors in their RNA code that lead to slightly different versions of the virus in the next round of replication. Each error is a mutation that may lead to a structural change in one of the viral proteins when one amino acid building block is swapped for another or deleted. In this way, evolution sculpts the shape and function of the virus, while natural selection ensures the best-adapted versions are more likely to proliferate. Mutations that serve the virus well tend to arise again and again.

A glance at the genome of Omicron shows it is carrying several mutations first seen earlier in the pandemic, along with many more that are new. It’s this combination of old classics and novelty that has sparked concern and pre-emptive measures such as travel bans, though it’s not clear yet exactly what all those mutations portend.

Among the older mutations is one known as D614G. The label means that, at position number 614 of the long amino acid chain that makes up the virus’s spike protein, an amino acid designated D (aspartate) has been swapped out for a G (glycine), causing a modest change to the shape of the protein. Every other variant of concern features this chain, as does the version of the coronavirus that emerged in Europe and, in Canada, quickly overtook the version first seen in Wuhan, China, in early 2020. More than a year and half later, researchers are still studying this change, one of the first noteworthy mutations to have been spotted during the pandemic.

When the first three variants of concern emerged, scientists noticed that all of them carried a mutation known as N501Y, which produces a change in the part of the spike protein that makes direct contact with host cells. In addition, Beta and Gamma featured another mutation, E484K, which is thought to help the virus evade the body’s immune response. Yet Delta showed that there is more than one way to build a more powerful variant. It carries neither N501Y or E484K yet it has handily defeated all the other variants in head-to-head competition.

Omicron does have N501Y, along with some other previously seen mutations that are not present in Delta. Importantly, one of those mutations is a deletion that had previously been used to identify the Alpha variant in rapid screening tests. That means the same test can now be repurposed to spot Omicron in samples from travellers and other individuals who test positive for COVID-19.

But it’s all the other mutations that currently hang over the response to Omicron and have left experts hoping for the best while preparing for the worst in terms of the potential effects on transmission, disease severity or vaccine effectiveness.

The problem for public-health officials is that by the time scientists know for sure what all the changes mean – which could take weeks or months – critical decisions about how to respond will already have been made. And past experience has shown that it’s a risky proposition to wait and see what a variant will do.

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