Multiple SARS-CoV-2 variants that have higher transmissibility, cause more severe disease, or that can evade immunity to some extent have been detected and tracked since late 2020. The Delta variant, for instance, is thought to be more transmissible than other SARS-CoV-2 variants and to result in reduced vaccine effectiveness.

The US CDC currently defines three classes of SARS-CoV-2 variants: variants of interest, variants of concern, and variants of high consequence.

• Variant of interest (VOI): “variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.” As of the most recent CDC update on 27 July, there are six VOIs: B.1.427, B.1.429, B.1.525, B.1.526, B.1.617.1, and B.1.617.3.
• Variant of concern (VOC): “variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.” As of the most recent CDC update on 27 July, there are four VOCs: B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and P.1 (Gamma).
• Variant of high consequence (VOHC): “variant that has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.” As of the most recent CDC update on 27 July, there are no VOHCs.

A VOHC, in addition to having attributes of a VOC, might cause the following:

• Demonstrated failure of diagnostics
• Evidence to suggest a significantly reduction in vaccine effectiveness, a disproportionately high number of vaccine breakthrough cases, or very low vaccine-induced protection against severe disease
• Significantly reduced susceptibility to multiple Emergency Use Authorization (EUA) or approved therapeutics
• More severe clinical disease and increased hospitalizations