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Omicron (B.1.1.529) Characteristics

WHO Label:  Omicron

Pango Lineage:  B.1.1.529

Nextstrain clade:  21K

 The spike protein of the Omicron variant is characterized by at least 30 amino acid substitutions, three small deletions, and one small insertion. Notably, 15 of the 30 amino acid substitutions are in the receptor binding domain (RBD). There are also a number of changes and deletions in other genomic regions.

  • Key Amino Acid Substitutions in Spike Protein (RBD substitutions in bold type): A67V, del69-70, T95I, del142-144, Y145D, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F

Transmissibility:  Currently, it is unknown how efficiently the Omicron variant can spread from person to person. The replacement of Delta by Omicron as the predominant variant in South Africa raises concerns that the Omicron variant may be more transmissible than Delta, but due to the low number of cases in South Africa when Omicron emerged, it is unclear if this variant is more transmissible than the Delta variant. Further, the relatively small number of cases documented to date makes it difficult to estimate transmissibility. Analysis of the changes in the spike protein indicate that the Omicron variant is likely to have increased transmission compared to the original SARS-CoV-2 virus, but it is difficult to infer if it is more transmissible than Delta.

  • N501Y increases binding to the ACE2 receptor, which could increase transmission, and the combination of N501Y and Q498R may increase binding affinity even more; however, other substitutions in the Omicron spike protein are expected to decrease binding to ACE2. As such, receptor binding affinity needs to be assessed using the full spectrum of spike protein substitutions found in the Omicron variant.
  • H655Y is proximal to the furin cleavage site and may increase spike cleavage, which could aid transmission.
  • N679K is proximal to and adds to the polybasic nature of the furin cleavage site, which may also increase spike cleavage and could aid transmission.
  • P681H has been shown to enhance spike cleavage, which could aid transmission. This mutation is found in Alpha and an alternate mutation at this position (P681R) is found in Delta.

Disease Severity:  Currently, it is unclear if infection with the Omicron variant is associated with more severe disease. Due to the small number of cases attributed to the Omicron variant, assessment of disease severity is difficult. Preliminary information from South Africa indicates that there are no unusual symptoms associated with Omicron variant infection, and as with other variants, some patients are asymptomatic.5

Impact on Vaccine-Induced Immunity or Immunity from Previous Infection:  Currently, there are no data available to assess the ability of sera from vaccinated persons or those with previous SARS-CoV-2 infection to neutralize the Omicron variant. However, the U.S. Government SIG and global public health partners are working to generate these data in laboratory settings and will also continue to monitor epidemiological and clinical indicators.

The spike protein is the primary target of vaccine-induced immunity. The Omicron variant contains more changes in the spike protein than have been observed in other variants, including 15 in the RBD. Based on the number of substitutions, the location of these substitutions, and data from other variants with similar spike protein substitutions, significant reductions in neutralizing activity of sera from vaccinated or previously infected individuals, which may indicate reduced protection from infection, are anticipated.

Laboratory and epidemiological studies are needed to assess the impact of the Omicron variant on vaccine effectiveness and breakthrough infections, including in individuals who have received booster doses. However, vaccination is anticipated to continue to offer protection against hospitalization and death, and vaccines continue to play a critical role in controlling the COVID-19 pandemic.

Impact on Monoclonal Antibody Treatments:  Currently, there are no virus-specific data available to assess whether monoclonal antibody treatments will retain efficacy against the Omicron variant. Based on data from other variants with significantly fewer changes in the RBD, the expectation is that the Omicron variant will remain susceptible to some monoclonal antibody treatments, while others may have less potency.

Mutations within the RBD are most relevant for monoclonal antibody therapeutics available under Emergency Use Authorization (EUA). Currently, there are three monoclonal antibody treatments with EUA:  Sotrovimabexternal icon, Bamlanivimab and Etesevimabexternal icon, and REGEN-COVexternal icon.

The table below shows data only for single RBD substitutions that are within the binding site of the indicated monoclonal antibody. However, mutations in the monoclonal antibody binding site do not always result in a loss of binding or neutralization. Importantly, data are needed with the full spectrum of spike protein changes to understand the impact on available monoclonal antibody therapeutics. As data becomes available, the Department of Health and Human Services will rapidly communicate changes in treatment guidance to public health departments and health care providers, as appropriate.

Source of original article: Centers for Disease Control and Prevention (CDC) / 2019 Novel Coronavirus (tools.cdc.gov).
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