December 5, 2021

Coronavirus FAQ: Help me with omicron vocab. What's immune evasion? Epistasis?

 NPR

A 3D-generated image of the coronavirus variant of concern known as omicron. The little bumps are spike proteins (see definition below).

Uma Shankar Sharma/Getty Images

When I'm reading about the new omicron variant, I feel like I need a medical degree. What does "immune evasion" mean, exactly? Virus neutralization assay?! Help!

We get it: COVID-19 news happens fast, and those of us without a medical degree can feel a little lost. So we turned to three COVID-wise experts — Dr. Jill Weatherhead, assistant professor of adult and pediatric infectious diseases at Baylor College of Medicine; Dr. Greg Poland, professor of medicine and infectious diseases at the Mayo Clinic in Rochester, Minn.; and Matthew Binnicker, Ph.D., vice chair of practice in the Department of Laboratory Medicine and Pathology at the Mayo Clinic — to help us translate some of the terms you're likely to run across.

So let's start with a quote from Weatherhead:

"The omicron variant has over 50 genetic mutations in the viral genome. Many of these mutations are found in the spike protein region," Weatherhead says. "Some of the individual mutations suggest that the omicron variant may be more transmissible or evade immune responses. Despite the association of these mutations with transmissibility and immune evasion, the clinical impact of omicron remains unknown because of the phenomenon of epistasis."

If you didn't quite catch all of that, here's a guide to help.

Mutation: A mutation is a change in a virus's genetic code. Mutations are a normal part of viral replication. Viruses make copies of themselves as they spread within a human. Mutations happen when a mistake is made during copying. In rare instances, mutations change the behavior of the virus. Most of the time, they don't.

Variant: In essence, a variant is a version of the virus with a slightly different genetic sequence because of the appearance of mutations. Many mutations quickly disappear as the virus spreads. But sometimes, mutations stick around and get passed down to future generations of the virus. Over time, the virus can accumulate a unique set of mutations that make it distinct from other versions of the virus. These distinct versions are called variants.

Variant of concern (VOC): The World Health Organization and the Centers for Disease Control and Prevention monitor variants and alert the public to variants of concern that could pose added risk because of "increased transmissibility, increased severity of disease or decreased effectiveness of public health interventions [diagnostic tests, preventive measures like vaccines or therapeutic measures like monoclonal antibodies]," Weatherhead explains.

Transmissibility: The ability of a virus to spread from infected people to others. The delta variant is more transmissible than previous variants because of mutations on its spike protein, which make it better at attaching to and infecting cells. There is concern that omicron could be even more transmissible than the highly transmissible delta variant, but we don't know yet whether that is the case.

Immune evasion: After an infection or a vaccine, your body produces antibodies that can detect and kill the virus upon a subsequent exposure. Sometimes a virus can mutate in a way that helps it evade or escape detection by those antibodies. That's what scientists call "immune evasion." There's preliminary evidence that omicron could be much better at immune evasion than the delta variant or any other variant before it because of the specific mutations on its spike protein.

Outcompete: In sports, if you outcompete other athletes by getting to the finish line first or scoring more points, you're No. 1. In the world of viruses, winning is more akin to the reality show Survivor; viruses can evolve to infect more people — or to infect them faster — than previous variants and become No. 1. "It's basically survival of the fittest," Binnicker explains. "Delta showed us it was king of the hill. We'll have to see over the next two to four weeks if omicron is better at transmitting than delta." If it is, it will likely push delta out of many regions of the world and could become the dominate variant.

Epistasis: The Greek roots of this word mean "standing upon." So what does that have to do with viruses? Well, in genetics, the term describes how mutations depend on each other. The way an individual mutation makes a virus behave often depends on what other mutations are present. That's why scientists can't look at a single mutation and know exactly how it will change a virus — mutations need to be assessed together. Think of it as cheerleaders standing on each other: Any movement by one of them often affects the entire formation.

Virus neutralization assay (VNA): OK, let's take this apart. An assay is a test. Neutralization is a term familiar to those who love science fiction. If you neutralize an attack from an alien ship, you've won! In the world of viruses, we want to know if antibodies can stop — or neutralize — a virus particle. And the way to find out is a VNA: a lab test that measures the capability and magnitude of a human's antibodies to stop infection. This test can be used to determine how well one part of the immune system is working to prevent or clear an infection. Scientists can use it to estimate how well a vaccine may work.

Hybrid immunity: Scientists say a person has "hybrid immunity" if the person was infected with SARS-CoV-2 and then, at least six months later, received a COVID-19 vaccine. This scenario triggers high levels of antibodies and strong protection against variants. Some scientists have called it "super-immunity."

Spike protein: You've probably seen more than enough pictures of the SARS-CoV-2 virus. The spike protein creates the bumps on the virus particle. It's a critical region of the virus for several reasons. Spike proteins bind to human cells and help the virus gain entry inside cells. And these spike proteins are the target of many critical antibodies. A major way the immune system detects the virus is by its spike proteins.

Preventive measures: OK, this isn't a hard one to figure out. And for now, the fact remains that not enough is known to take much action to forestall infections besides getting vaccinated and boosted and following the prevention strategies of masking and physical distancing that we've relied on throughout the coronavirus pandemic.