• COVID-19

    SARS-CoV-2 mutations explained

A year after the first case of COVID-19 was reported in the U.S., more than 26 million Americans are confirmed to have had this disease, caused by the SARS-CoV-2 virus. More than 104 million cases have been confirmed globally.

During that time, researchers have tracked changes to the virus' genome through positive COVID-19 samples collected for surveillance or testing, and shared that information in a public database. These changes are called mutations. They are uncovered through a process called sequencing, where viral RNA is examined to determine its genetic makeup. Then, the sequence of the potential variant is compared to the original sequence in the database. This helps to show how the virus is changing over time; in essence, creating something like a family tree.

And each of us can act as a host for a viral family reunion.

"You get infected by a population of viruses," says Richard Kennedy, Ph.D., an immunologist and co-director of Mayo Clinic's Vaccine Research Group. "Each individual virus could be different from the others because mutations happen at random locations."

Richard Kennedy, Ph.D., studies the development of immune responses after vaccination in order to understand why some individuals develop hearty immunity while others do not. Read more about his work on his research description page.

In a person with active infection, some of these mutations have no effect on the virus, and they blip in and out of the virus population. The ones that make the virus less able to spread are eliminated from the population. But there are some that may help it spread. As part of the immune response, the body makes a variety of antibodies, all of which bind to a small piece of viral protein. If the virus mutates, the protein made from those instructions might change enough that the antibody can't bind to it or binds less tightly.

"The mutations that help the virus gradually accumulate within the person and have a greater chance of being transmitted to someone else," says Dr. Kennedy. "The current South African variant is able to evade some, but not all, of the antibody response to vaccination, and a Brazilian variant has the same mutations."

One thing is for sure, says Dr. Kennedy, "Mutations will continue. We will see more variants arise."

And that's down to biology. If someone has antibodies due to vaccination or prior infection, then any mutations that help a virus escape those antibodies will help the virus spread. If a person has a lot of antibodies, then the virus is more likely to be destroyed before it can mutate. As a new-to-humans virus, there is a lot more we need to know about SARS-CoV-2, says Dr. Kennedy.

SARS-CoV-2 (red dots) on the surface of a cultured Vero cell (nucleus is at the bottom left). Image courtesy of the Mayo Clinic Microscopy and Cell Analysis Core.

"Our immune system doesn’t make just one antibody to fight off an infection, it makes dozens," he says. "This makes it harder for the virus to mutate to avoid all of them. The antibody response to a single dose of these messenger RNA vaccines is much lower than it is after two doses. We don't know if only getting one dose of a two-shot vaccine creates enough antibody to cause mutation pressure but not enough to protect us. Another point to consider is that immunity wanes with time, and protection will likely decline even after getting vaccinated with two doses."

Dr. Kennedy says that researchers are actively investigating specifics, such as how long antibodies stick around in an individual and what level and type of antibodies are associated with the longest-term protection. Researchers also are looking at how quickly these variants spread, and if mutations make a disease more or less severe. Other necessary information is if the current tests for COVID-19 pick up the mutated viruses and if medication currently in use is still effective.

The good news is that everything researchers have learned in the last year sets up the scientific community to respond with swiftness. Vaccine companies are now looking at how to tweak current vaccines to account for variants. For all of us following the news of variants, Dr. Kennedy has some advice.

"Masking, social distancing and hand-washing will all decrease our chance of exposure, no matter what variants are out there," he says. "If we follow all the recommendations for masking, distancing and hand-washing, and get a COVID-19 vaccine when it is offered to us, we will have multiple layers of protection in place to keep us safe."

— Sara Tiner, February 19, 2021