As the highly-contagious Delta variant sprinted around the world — in many countries quickly establishing itself as the dominant strain of the SARS-CoV-2 virus — it helped illustrate both the potential dangers of new variants and the fragile victory achieved through vaccination. As the World Health Organization adds to its list of variants, with Kappa and Lambda recently joining the ranks, there is widespread fear that the next mutation could find a chink in the vaccines’ armor. For some infectious disease experts, those fears are stoked further by the fact that so many populations are only partially vaccinated, if at all, which could provide the right circumstances to spur the evolution of a vaccine-resistant strain.

So far, though, the nightmare scenario has not materialized. And with a better understanding of variants, vaccines, and viral evolution, we might be able to diminish our fears and tackle pandemic management head-on.


Where do variants come from?

Let’s start with a few basics. Genetic mutations typically arise when the DNA or RNA of an organism is copied imperfectly. Anytime your cells, or any cells, divide, they have to make a copy of their DNA; and the enzyme responsible for producing that copy occasionally makes a mistake, altering the gene sequence ever so slightly. Most of the time these mistakes are meaningless. But once in a great while, one of those changes will have a noticeable effect.

Viruses don’t have the genetic machinery to copy their own genomes. They can only reproduce by hijacking another organism’s cells and forcing them to churn out copies of the virus. This means two important things: first, viruses can’t multiply or evolve without a host; and second, new copies of each virus are subject to the same genetic mistakes our cells’ genetic machinery sometimes makes.

In the COVID-19 pandemic, every infected person offers the virus a chance to evolve through the accumulation of mutations. Most mutations won’t make a difference, but some will serve the virus in some way — such as making it hardier, more contagious, or resistant to our natural immune response. Mutations that give the virus an advantage are more likely to survive over time, becoming new variants that may get the opportunity to sweep through populations.


Why are some variants so dangerous?

The genetic mistakes fueling new variants occur randomly, but certain situations provide just the right ingredients to make it more likely that a virus will mutate into something stronger. Known variants of concern, such as Alpha, Gamma, and Delta (originally detected in the UK, Brazil, and India, respectively) are believed to have evolved within individual patients suffering prolonged COVID-19 infections. Within those hosts, the virus would have been under tremendous pressure from each person’s immune response and possibly from medications given over time. These pressures essentially force the virus to mutate faster, as it attempts to remain active in that individual. Any strain of the virus that’s susceptible to the immune response or therapies is stymied, while the strains that survive likely have advantageous mutations that allow them to evade these threats. If that patient manages to spread the virus to someone else, the variant transmitted is likely to be stronger, more contagious, or resistant to treatment. Such variants have a competitive advantage over other strains of the virus in the human population, allowing them to become dominant.

Why are low vaccination rates problematic?

In infectious disease, vaccines are incredibly effective when enough people in the population are protected that the entire group achieves “herd immunity.” At that point, even if someone in that population gets infected, the chances of that person transmitting the virus to another member of the group are minimal.

Populations that are only partially vaccinated, though, are another story. Without herd immunity, a mix of vaccinated and unvaccinated people can actually give the virus the conditions to acquire mutations that allow it to resist the immune response triggered by vaccines. Whereas with herd immunity a single infection has virtually no one else to jump to, in a group that’s partially vaccinated there can still be a fair amount of transmission. That makes it more likely that sometimes even people who have been vaccinated will become infected (though their infections so far have been shown to mostly be mild or even asymptomatic). But if the virus evolves in vaccinated people, the variants that survive and get passed back into the population can have a better chance of carrying mutations that allow them to evade vaccine-induced protections. “Letting a virus rip through a partially vaccinated population is exactly the experiment I’d do to evolve a virus able to evade immunity,” said University of Liverpool geneticist Steve Paterson in a recent tweet.

In places like the U.S., where some regions are highly vaccinated and others have much lower rates, there could thus be higher risk that the virus will randomly acquire mutations that allow it to sneak past our vaccine-trained defenses. The same is true when there are people available for a variant to infect who have only gotten one dose of a two-dose vaccine. Most vaccines target the virus’s spike protein, so a mutation altering that protein just enough to render it unrecognizable by our immune system could lead to a variant resistant to the vaccine.

What’s the best way to prevent new variants?

Nobody can stop the evolutionary process that causes the virus to mutate. What we can do is give the virus fewer chances to mutate by preventing transmission. The single best way to do that is to get fully vaccinated — in the U.S., that’s with two doses of the Pfizer/BioNTech or Moderna vaccines or a single dose of the Johnson & Johnson vaccine. Wearing a mask also of course helps by making transmission harder for any strain.

Most experts believe that concerns about the vaccines’ effectiveness against the Delta variant are overblown. While a recent study in Israel showed only 64% effectiveness for the Pfizer vaccine, the study design was not ideal and other, larger studies have repeatedly demonstrated numbers closer to 90%.

Where vaccines are less accessible, and also in partially vaccinated populations, measures such as wearing masks and keeping a distance will continue to be helpful for reducing transmission and preventing the emergence of new variants.