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Coronavirus Variants: How Much Do You Need to Worry?

First: What exactly is a SARS-CoV-2 variant?

The virus that causes COVID-19, SARS-CoV-2, has about 30,000 letters in its genome (the total genetic material of the virus). When it replicates, some of these letters change by mistake. “Any single letter change is a variant,” explains Dr. Osmundson. Most of these changes won’t make a difference in how the virus behaves. “Some mutations may lead to an inactive virus,” Dr. Osmundson says. “Very rare variants may act measurably different from the original strain.” The original strain is typically referred to as the “wild type” virus. Sometimes, a variant that behaves differently can provide the virus with an advantage over its wild type counterpart, like being able to spread more easily.

While a virus with even a single mutation is technically a new variant, many variants contain multiple mutations. These are identified by sequencing the entire genome of the virus and looking for places that don’t match up with the wild type virus. A letter may be different or missing altogether. Viruses that have the same collection of mutations are then given names to distinguish them from the wild type. “Other viruses that are sampled and that have the same mutations are considered part of that 'variant,’” Dr. Hodcroft explains.What variants are out there right now, and why are they concerning?

We’re currently looking at an alphabet soup of different variants in SARS-CoV-2. There are two garnering the most attention. One concerning variant was first found in the U.K. and is known as B.1.1.7 and sometimes as 501Y.V1 (the latter designation refers to one of the key mutations it contains). The B.1.1.7 variant contains 23 mutations that differentiate it from the wild type virus. Another variant that's causing concern, 501Y.V2, recently emerged in South Africa and has at least 21 mutations that have changed from the wild type. (Unlike B.1.1.7, it hasn't yet been detected in the U.S.)

Both of these coronavirus variants have mutations in the SARS-CoV-2 spike protein, which is a key coronavirus protein. The spike protein is what enables the virus to get into a person’s cells and replicate, causing infection. The B.1.1.7 variant has received the lion’s share of attention to date because it appears to increase viral transmission compared to the wild type. Dr. Hodcroft notes that this variant (and 501Y.V2, to a lesser extent), have been “associated with worrying rises in cases.” Dr. Osmundson agrees with this concern. “Epidemiological data from different populations show an increase in the transmission of 50-70%,” he says. “This has yet to be confirmed in animal models and across broader epidemiological data. It's strong preliminary data.” A Centre for Mathematical Modelling of Infectious Diseases study released from the U.K. (but not yet peer-reviewed) suggests that the B.1.1.7 variant is “56% more transmissible” than pre-existing SARS-CoV-2 viruses in the country, but Dr. Osmundson notes we don’t know yet exactly why the virus is easier to spread. “Tighter binding to host cells? Higher viral titers in the nose or throat leading to more shedding? Faster/better viral replication? We have no data here whatsoever.”Will COVID-19 vaccines still work against these variants?

The authorized vaccines from Pfizer/BioNtech and Moderna target that important spike protein using mRNA technology. Since the B.1.1.7 and 501Y.V2 variants involve mutations to the spike protein, some experts are concerned that the variants may be able to prevent immunity, either from natural infection or from immunization. The most concerning spike protein mutation in the B.1.1.7 variant from the U.K. is dubbed N501Y, while the 501Y.V2 variant first found in South Africa has a spike protein mutation labeled E484K. In a not-yet-published study, researchers found that in 21 of 44 people who got coronavirus in the first wave of infection in South Africa, their antibodies didn’t recognize 501Y.V2. Though this isn’t definitive proof that this variant can escape immunity, it bears watching and additional testing.

Pfizer has already tested a number of spike protein mutations and recently reported that their vaccine seemed to still be effective against the most worrisome spike protein mutation in B.1.1.7. They also tested 15 other spike protein mutations, and “none of them have really had any significant impact” on the vaccine’s effectiveness, a Pfizer vaccine scientist told Reuters. (Moderna is currently carrying out similar testing with their vaccine). Notably, Pfizer hasn’t yet tested the spike protein mutation in 501Y.V2, and there is some preliminary data (not yet peer-reviewed) suggesting that mutation may be a better candidate for escaping immunity. But Dr. Hodcroft cautions: “It is hard to predict how lab results translate to real life, as the systems are much more complex.”

The next two vaccines that seem likely to get authorized—one from Johnson & Johnson, the other from Oxford/AstraZeneca—work differently from the Pfizer/BioNTech and Moderna vaccines. But they both rely on the viral spike protein, meaning mutations to that protein could theoretically affect these vaccines’ effectiveness similarly.

Should we worry about other variants?

While the B.1.1.7 and 501Y.V2 variants may be the most scrutinized currently, we’ve seen other variants come and go—a pattern likely to persist as the pandemic continues. Dr. Hodcroft worked on an analysis of a variant in Spain, 20A.EU1, that spread across Europe in summer 2020. In that case, the increased spread of the variant seemed to be unrelated to any particular mutation in the virus that made it more transmissible. Instead, researchers chalked it up to human behavior, including travel. Dr. Hodcroft notes, “this shows that human behavior is incredibly important. [20A.EU1] is the most prevalent variant in Europe right now, and it didn't need higher transmission to get there.”

Another variant experts are examining is one from Brazil, B.1.1.28. This variant contains the same E484K mutation as the variant from South Africa and appears to have caused COVID-19 reinfection in a health care worker in Brazil. “Home-grown” variants appear to have originated in California and Ohio as well and may be linked to increased transmission, but those variants need additional testing and characterization for us to know for sure.