(NEXSTAR) — Numerous SARS-CoV-2 variants have circulated in the United States since the beginning of the pandemic, but none have met the government’s criteria for the most concerning classification: “Variants of High Consequence.”

“Variants of High Consequence” (VOHC) is one of four designations used to classify variants by the SARS-CoV-2 Interagency Group (SIG), which was established by the U.S. Department of Health and Human Services after the onset of the COVID-19 pandemic. The SIG’s other classifications include Variants Being Monitored (VBM), Variants of Interest (VOI) and Variants of Concern (VOC).

Those last three terms — VBM, VOI and VOC — may sound more familiar, seeing as the World Health Organization (WHO) uses the same terms for its classifications of SARS-CoV-2 variants.

WHO does not, however, use the classification of “Variants of High Consequence” like the SIG. (WHO and the SIG also do not categorize the same major SARS-CoV-2 variants under the same classifications for VBM, VOI and VOC, mostly because WHO is concerned with global risk, whereas the SIG is assessing risk within the U.S.)

So what exactly is a Variant of High Consequence? First, it’s important to understand the attributes belonging to variants in lower classifications.

Variants Being Monitored

The CDC, another agency under the Department of Health and Human Services, defines VBMs as variants that “do not pose a significant and imminent risk to public health.” These variants could have been associated with severe disease or increased transmission, but are no longer circulating widely, or do not pose as much of a risk due to “authorized medical countermeasures.”  

Variants currently in this category include the alpha, beta, gamma and epsilon variants, all of which were at one time classified as Variants of Concern before being reclassified by the SIG. Current VBMs also include eta, iota, kappa, B.1.617.3 and zeta (all classified as Variants of Interest at one time) and the mu variant.

Variants of Interest

VOIs have “specific genetic markers” that make them more of a threat to public safety, possibly by having attributes suggesting a risk of increased severity, increased transmission, reduced efficacy of therapeutics or treatment, or “potential diagnostic impact,” according to the CDC. There may also be evidence that the variant is responsible for an increase in cases or a cluster of outbreaks, among other attributes.

There are currently no variants classified as VOIs by the SIG. Those that were previously classified as VOIs have since been reclassified into other categories (see above).

Variants of Concern

VOCs are those that meet the criteria of a VOI, but may also show evidence that associates them with more severe disease or increased transmissibility. Therapies, diagnostics, vaccines, or antibodies generated from previous COVID infections may also show significantly reduced effectiveness against a VOC.

Current VOCs, as classified by the SIG, include delta and omicron.

Variants of High Consequence

VOHCs may demonstrate some of the attributes of a VOC, but show more “clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants,” per the CDC.

Other characteristics of a VOC may include evidence of a reduction in vaccine effectiveness or “very low vaccine-induced protection,” as well as an increase in “more severe clinical disease and increased hospitalizations.”

No SARS-CoV-2 variants have been classified as VOHCs.

Researchers, meanwhile, say it’s difficult to predict where and when a new variant will emerge, or whether it may pose a greater health risk to the population.

“If viral evolution were logical, which it is, kind of, we would expect … the variants that would survive and thrive would be more transmissible or more immune evasive,” George Rutherford, an epidemiologist at the University of California, San Francisco, previously told Nexstar. But there’s also “no premium” for a virus to kill off its host immediately, he said, as that wouldn’t be an efficient way for the virus to spread.

Rutherford warned, however, that virus mutations won’t always follow the most logical path.

“Be prepared,” he said. “The [next mutation] could be something that’s very different.”