The Omicron variant of coronavirus SARS-CoV-2, also known as B.1.1.529, was first reported to WHO from South Africa on November 24, 2021. The variant was detected during a steep increase in SARS-CoV-2 infections and was collected on November 9, 2021. The Omicron variant was identified around the same time in individuals in Botswana, South Africa and a traveler from South Africa visiting Hong Kong. These SARS-CoV-2 genomes were designated as belonging to a new PANGO lineage, B.1.1.529 on November 24, 2021. The Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE) advised WHO that the variant be designated as a VOC and the WHO designated B.1.1.529 as VOC named Omicron.
Omicron is made up of several sublineages, which include BA.1 (B.1.1.529.1; original omicron variant), BA.1.1 (B.1.1.529.1.1; Nextstrain clade 21K), BA.2 (B.1.1.529.2; Nextstrain clade 21L), BA.3 (B1.1.529.3), and BA.4. BA.2 has a growth advantage and appears to be more transmissible compared with BA.1. The difference in transmissibility between BA.1 and BA.2 appears to be smaller than the difference between BA.1 and Delta. Reinfection with BA.2 following infection with BA.1 has been documented, but population-level reinfection studies over a limited period of time suggest that infection with BA.1 provides strong protection against reinfection with BA.2. BA.2 was reported to not likely to cause more severe disease.
BA.1 made up more than 97% of omicron variant sequences worldwide in November and December 2021. An upsurge of BA.2 occurred in early January, 2022 in Europe and Asia and as of January, 2022 this omicron variant accounted for 15.6% of sequences. As of March, 2022, BA.2 was reported to account for up to 70% of new infections in parts of the US, as estimated by the genomics company Helix. The CDC reported that BA.2 accounted for 35% of coronavirus infections nationally as of March 26, 2022. As of March 29, 2022, BA.2 was reported by the WHO to represent almost 86% of cases worldwide. One possible reason for the global rise in BA.2 is the co-occurrence of lifting of public health interventions in many countries.
BA.2 is referred to as the stealth variant because it is slightly more difficult to track. BA.1 was tracked by the absence of one of the genes in PCR testing. BA.2 and BA.3 will test positive on PCR tests but will not be distinguishable from previous SARS-CoV-2 variants. BA.2 and BA.3 can only be identified by genomic sequencing.
The original Omicron variant has more than fifty mutations compared with the original SARS-CoV-2 virus isolated in Wuhan, China. Thirty of these mutations correspond to changes in amino acids in the spike protein, which is used by the coronavirus to attach and fuse with cells in the respiratory tract. Previous variants of concern had no more than 10 spike mutations.
Some of the mutations in Omicron were found in previous variants of SARS-CoV-2. These mutations were known to increase the ability of the virus to bind to the ACE2 receptor protein on host cells or help it evade the immune system. Compared with previous variants, Omicron binds stronger to ACE2 and is better at evading neutralizing antibodies from the immune system of people who have been vaccinated or previously infected by earlier variants.
Other changes in the spike protein are thought to make Omicron less adept at fusing directly with the cell membrane and result in the virus gaining entry after being engulfed in an endosome. This difference in viral entry can be explained by the fact that previous variants used two proteins, ACE2 and TMPRSS2, to fuse to the cell membrane and inject viral genetic material into the cell. Omicron uses only ACE2 to get inside cells and is able to infect more types of cells. Whereas other variants infect and replicate in the lungs, Omicron readily infects and replicates in cells of the airway above the lungs. More than twelve of Omicron’s mutations are rare and had not been seen in previous variants of SARS-CoV-2.
The above figure, a schematic diagram of spike mutations in five variants of concern derived from data from https://covariants.org (20I for Alpha, 20H for Beta, 20J for Gamma, 21A for Delta, and 21K for Omicron, respectively), was published in He X, Hong W, Pan X, Lu G, Wei X. SARS-CoV-2 Omicron variant: Characteristics and prevention [published online ahead of print, 2021 Dec 16]. MedComm (2020). 2021;2(4):838-845. doi:10.1002/mco2.110.
BA.2 has fewer mutations than BA.1 with thirty-one mutations on the spike protein. As of February 3, 2020 there were 400 cases of BA.3 around the world in nineteen countries. BA.3 has thirty-three mutations in the spike protein, with thirty-one of spike protein mutations shared with BA.1. The other two spike protein mutations are shared with BA.2.
The above image is a Venn diagram showing similarities and differences between Omicron family viruses BA.1, BA.2 and BA.3. (Access Health International).
BA.4 has four confirmed sequences in South Africa, one in the US and one in Puerto Rico in the GISAID (Global Initiative on Sharing All Influenza Data) database as of March 16, 2022. BA.4 may be a recombination event between BA.1 and BA.3. Mutations unique to BA.4 are in NSP15 (N11S) and the N-terminal domain of the Spike protein (L212I). Nsp15 is a uridine specific endoribonuclease conserved across coronaviruses that processes viral RNA to evade detection by host defense systems. These two mutations are proposed to have arisen in BA.4 post-recombination.
BA.1 infection is generally associated with lower severity, but the increased transmissibility compared with delta resulted in high numbers of patients admitted to hospital. BA.1 is associated with a 5.4-fold higher re-infection risk than delta.
Covid vaccines available as of February 2022 appear to provide strong protection against severe disease and death from BA.1. Two doses of covid vaccine reduced effectiveness against milder disease caused by BA.1, compared with previous variants. The third booster dose was reported to provide greater protection against BA.1 compared with two doses.
Treatments ronapreve (casirivimab and imdevimab) were found to have reduced efficacy against BA.1. In lab experiments, sotrovimab seemed to retain activity against the BA.1 spike protein. Molnupiravir was also found to retain activity against BA.1 in preclinical studies.
The UK Health Security Agency (UKHSA) reported that BA.2 had an increased growth rate across England, compared with BA.1. Contact tracing data showed that people infected with BA.2 were more likely than people with BA.1 to infect household contacts. UKHSA found no evidence of reduced vaccine effectiveness against symptomatic disease for BA.2 compared with BA.1. Vaccine effectiveness against symptomatic infection was reported as 13% for BA.2 and 9% for BA.1 at least twenty-five weeks after two doses, and 70% (BA.2) and 63% (BA.1) at two weeks following a third booster dose.
