- Lucy van Dorp, PhD, Lucy van Dorp, PhD, is a senior research fellow at the University College London Department of Genetics, Evolution & Environment.
- Richard B. Kennedy, PhD, Richard B. Kennedy, PhD, is a virologist and vaccine researcher at Mayo Clinic in Rochester, MN
- Theodora Hatziioannou, PhD, Theodora Hatziioannou, PhD, is a virologist and research associate professor at Rockefeller University.
How and why viruses mutate
When you get sick with a virus like the novel coronavirus, “it’s not really a single virus [particle] that infects you. It’s a population of viruses,” explains Richard Kennedy, PhD, a virologist and vaccine researcher at Mayo Clinic in Rochester, MN. You might get infected by 100 or even 10,000 different viral particles. Each particle has its own slightly different genetic code, much like any two people have slightly different genetic codes.
Changes in this code happen only when the virus replicates—aka makes copies of itself to survive. To replicate, a virus needs two things: a human cell (whose machinery it hacks to help itself replicate) and a specific enzyme it brings along to copy its genome (essential to the replication process). This enzyme acts as a cheap photocopier, Dr. Kennedy explains. “That photocopier is not a really good one. It makes mistakes left and right,” he adds. Those genetic mistakes end up being coded in the genome of all the new viruses created in that single infected cell.
These mistakes happen fairly regularly and randomly. Many come and go because they don’t give the virus any real advantage; some even make the virus less able to infect a cell. “Most mutations are expected to have no impact on the function of the virus or how we experience it,” says Lucy van Dorp, PhD, an expert in the evolution of pathogens and a senior research fellow at the University College London Department of Genetics, Evolution, and Environment.
Sometimes, however, a mutation creates an advantage for the virus. “Maybe the virus can infect other cells faster, or it attaches to cells a little better. It survives in the environment a little longer, or it produces more virus,” says Dr. Kennedy. Because all variants of the virus are trying to compete for the same number of cells that can be infected in a person’s body, beneficial mutations allow a variant to outcompete other viruses. Eventually, that strain becomes the predominant variant in a person’s body—and becomes the variant that’s spread to other people, Dr. Kennedy says.
How much a given mutation spreads from there depends on several factors, Dr. Kennedy explains, including how beneficial the mutation is to the virus and how many people can potentially catch the variant. “Most won’t go anywhere,” he says. “It’s the [variants] that show up, then are at 5 percent, 10 percent, 90 percent—those are the ones we’re worried about, because it suggests they have an advantage and that’s why they’re spreading through the population.” And given that, to date, there have been over 27 million coronavirus cases in the U.S. alone, that gives the virus plenty of time and opportunity to mutate—and for those more beneficial mutations to thrive.
The different strains of COVID-19 that scientists are watching
Scientists around the world track mutations (known as genomic surveillance) at different rates. The UK, for example, currently sequences the genome in 47.3 out of 1000 COVID-19 cases, while the U.S. sequences 3.23 out of 1000 cases. Tracking the virus’s genome allows scientists to identify and isolate new variants quickly and to update vaccines accordingly.
There are three strains that the U.S. Centers for Disease Control and Prevention (CDC) is actively watching, as they’ve all been found throughout the U.S. and so far appear to spread more quickly than other variants.
The United Kingdom (UK) variant B.1.1.7
First sequenced last fall and found in the U.S. by December, some researchers say the UK variant is 50 to 75 percent more transmissible than the original virus. “We’re paying close attention because it’s got several mutations to the spike protein," Dr. Kennedy says, referring to the unique protein structure on the outside of the coronavirus that's used to penetrate and infect cells. "There’s some evidence that makes that variant more transmissible—that people who are infected have more virus in them and their viral load is higher,” says Dr. Kennedy. Indeed, a January report from the CDC estimated that without further measures to check its spread, the U.K. variant could become the predominant variant in the U.S. by March.
Some researchers in the UK initially reported that this variant may be 30 to 40 percent deadlier than previous variants, although those studies are small and inconclusive. “Time will tell as we accumulate more information on the virus,” Dr. Kennedy says.
South Africa variant B.1.351
The South African variant shares some mutations with the UK variant. Some researchers have also voiced concerns about its ability to evade antibodies (proteins released by the immune system to attack foreign invaders like viruses), which potentially reduces the effectiveness of current vaccines.
“The South Africa variant has at least three mutations, and they’re right at the place where the spike protein binds to the cellular receptor,” says Dr. Kennedy. “That’s [the area] where neutralizing antibodies, either from infection or vaccination, are targeting." The concern, he says, is that mutations to that crucial location on the virus could help it avoid antibodies. If this theory pans out, it could mean that our current vaccines aren’t as effective (since it generates antibodies that might not be effective against that mutation), so you could get re-infected with this variant even if you’ve already been sick with or vaccinated against COVID-19.
Brazil variant P.1
With more mutations than either the UK or South African variant, the Brazilian variant may be better at dodging antibodies produced by the body to stamp it out, which could potentially make the virus deadlier. “The Brazil variant has the exact same three mutations in the spike protein [as the South African variant], so it’s likely that we’ll see a decreased neutralizing ability from that one, too,” says Dr. Kennedy. “Once we start vaccinating, if this starts to evade some of the vaccine protection, then it will still likely still circulate somewhat in the community. But what happens if it accumulates more mutations? That’s always the concern.”
What this means for vaccines
Everything about the new variations sounds concerning, but scientists stress that the different strains of COVID-19 shouldn't be keeping the average citizen awake at night. Indeed, some experts argue that we simply don’t have enough data yet to know how these new variants will affect us, period. “Neither increased transmissibility nor fatality of the new virus variants has been proven,” says Theodora Hatziioannou, PhD, a Rockefeller University virologist who’s studying the new variants.
Here's the lowdown on how vaccines work—including some of the newest COVID-19 vaccines:
Similarly, there is mixed evidence that these COVID-19 strains could affect the efficacy of the vaccines available. In January, biotech company Novavax reported its phase three coronavirus vaccine trial results. Its vaccine had nearly 90 percent efficacy in the U.S. and U. but only 60 percent efficacy in South Africa. “Part of that could be due to different populations and different underlying health conditions,” says Dr. Kennedy. “But it also might be because the South Africa variant was present.” Johnson & Johnson's phase three clinical trial results show that its single-dose vaccine was 72 percent effective in the U.S. but 57 percent effective in South Africa, where, the company noted, 95 percent of COVID-19 cases were linked to the South Africa variant at the time of the trial. And AstraZeneca just put its vaccine rollout in South Africa on hold after its trial found the shot provided “minimal protection” against mild to moderate cases.
“That’s already some data suggesting that vaccines won’t be as effective. But the flipside is 57 to 66 percent is a whole lot better than 0 percent,” adds Dr. Kennedy.
For now, the CDC says that the antibodies produced by the existing vaccines seem to recognize the major variants and thus would be capable of fighting them off. But more studies are underway to better understand how effective the vaccines in use and development are against these strains. Additionally, pharmaceutical companies are designing new vaccines to address the South Africa variant, while the Food and Drug Administration (FDA) is preparing a rapid review process for quick approval of booster shots if current shots are shown to be ineffective against new coronavirus variants.
“It’s going to be a continual race. What will probably happen is, much like influenza, we might have to have regular changes in the vaccine strain used, so we might need to get a COVID-19 vaccine every couple of years. They’ll just keep changing it to keep pace with the mutations,” says Dr. Kennedy. There’s good reason to hope, too, that existing vaccines will still tame the pandemic. Johnson & Johnson’s phase three trial, for example, found that people who did get sick after vaccination experienced less severe disease.
How to protect yourself
In a best-case scenario, approved vaccines will continue to be mass-produced and quickly distributed while scientists feed a continual pipeline of new and improved vaccines. The problem remains that scientists aren’t yet sure if vaccines prevent you from spreading the virus. “You could still have some virus in you and be able to transmit it, but you just don’t have any symptoms. That’s especially true given the fact that this virus is mutating, and already it’s evading at least some of the immune protection,” says Dr. Kennedy.
Since the only time the virus can mutate and produce new variants is when it infects a person, the only way to stop new variants from showing up and spreading is to reduce transmissions, says Dr. Kennedy. That means it’s critical for all of us to continue masking (or even double masking for stronger protection) and social distancing, even if we’ve already been vaccinated. “It’s painful, annoying, and uncomfortable, but if we want to beat this pandemic, that’s basically the only way to do it,” says Dr. Kennedy.
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