A study that monitored amino acid changes in the spike protein of SARS-CoV-2 included in a large sequence database identified a D614G (glycine for aspartic acid) substitution that became the dominant polymorphism globally over time. In animal and in vitro studies, viruses bearing the G614 polymorphism demonstrate higher levels of infectious virus in the respiratory tract, enhanced binding to ACE-2, and increased replication and transmissibility compared with the D614 polymorphism. The G614 variant does not appear to be related to a higher risk of hospitalization or to impact anti-spike antibody binding. It is now present in most circulating SARS-CoV-2 lineages, including the variants of concern listed below.

Delta — This lineage was first identified in India in December 2020 and had since been the most prevalent variant worldwide until the emergence of the Omicron variant.

The Delta variant is highly transmissible, more so than Alpha, which was more transmissible than previously circulating SARS-CoV-2 lineages. In reports from the United Kingdom, the proportion of SARS-CoV-2 infections caused by Delta rose as that caused by Alpha declined, and the secondary tribe infection rate related to Delta infection was 13.6 percent compared with 9.0 percent for Alpha. In another report of a small outbreak in the United States, the tribe attack rate connected with the Delta variant was 53 percent. The underlying mechanism for the increased transmissibility is uncertain. Data, some unpublished, suggest that upper respiratory viral RNA levels are higher at diagnosis and remain higher for longer with the Delta variant compared with the wild-type virus.

Infection with Delta may be linked with a higher risk of critical disease and hospitalization than with Alpha. As an example, in a cohort study of over 40,000 individuals with SARS-CoV-2 infection, 74 percent of whom were unvaccinated, the risk of hospitalization within 14 days of testing was higher among those with Delta compared with Alpha variant infection, although the absolute risk difference was small.

Several studies suggest that vaccine effectiveness is slightly attenuated against symptomatic infection with Delta but remains high against severe disease and hospitalization.

Omicron — This variant was first reported from Botswana and very soon thereafter from South Africa in November 2021. In South Africa, it was related to an increase in regional infections, and it was promptly identified in multiple other countries, where it was similarly connected with sharp increases in reported infections. As of late December 2021, Omicron accounted for the majority of new infections in the United States. The variant contains over 30 mutations in the spike protein, including mutations that have been found in other variants of concern and that have been related to increased transmissibility and decreased susceptibility to neutralizing antibodies.

Emerging data on the clinical impact of Omicron are preliminary and limited but suggest that Omicron has a replication advantage over the Delta variant and evades infection- and vaccine-induced humoral immunity to a greater extent than prior variants. Omicron appears to be corresponding with less severe disease than other variants, but this estimate is more uncertain.

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