Omicron is the fifth SARS-CoV-2 variant to be designated as a Variant of Concern (VOC) by WHO, following the designation of the Alpha, Beta, Gamma and Delta variants. The first known laboratory-confirmed case of Omicron was identified from a specimen collected on 9 November 2021 in South Africa, with the variant (Pango nomenclature B.1.1.529) first reported to WHO on 24 November. In consultation with the Technical Advisory Group on Virus Evolution (TAG-VE), WHO designated B.1.1.529 as a VOC on 26 November in view of the potential for enhanced transmissibility and/or a degree of immune escape, given the number of mutations (26-32) in the spike protein, as well as concerning initial epidemiological reports from South Africa, including signals of increased risk of reinfection. Here, we present an update on the current situation in terms of the epidemiology and transmissibility, clinical severity, risk of reinfection and the potential impact on diagnostics, vaccines and therapeutics.
As more data are analysed and understood about the potential implications that Omicron may have on the epidemiology, transmissibility, clinical severity, prevention and treatment of SARS-CoV-2 infection, our understanding of this variant will continue to evolve, and we will issue updates as further evidence becomes available.
Epidemiology
In South Africa, where Omicron was first reported, the case incidence of COVID-19 has continued to rise since the second week of November, with 62 021 new cases reported between 29 November and 5 December, a 111% increase compared to the previous week. An increase in the test positivity rate (TPR) has also been seen from 1.2% the week beginning the 7 November, to 22.4% the week beginning the 2 December. An initial increase in incidence in Gauteng province in mid-November was thought in part, to be due to a cluster of cases among students at a university. Very large increases in the weekly incidence of cases have also been seen in some countries neighbouring South Africa including: Eswatini (1990%); Zimbabwe (1361%); Mozambique (1207%), Namibia (681%) and Lesotho (219%). These other countries have very low vaccination coverage ranging from 12.1% of the total population fully vaccinated in Namibia to 26.7% in Lesotho. In South Africa 25.2% of the total population is fully vaccinated. While drivers of these increases remain unknown, it is plausible that spread of Omicron in combination with enhanced testing following the declaration of a VOC, play a role, together with the relaxation of public health and social measures (PHSMs) and sub-optimal immunization coverage.
Among countries in other regions reporting increasing spread of the Omicron variant, hundreds of cases of this variant have now been reported from countries in other regions. Since the last update published on 30 November, additional countries across all six WHO Regions have reported confirmed cases of the Omicron variant. As of 7 December 2021, the Omicron variant has been confirmed in 57 countries. However, given the predominant circulation of the Delta variant in many countries, particularly in countries in the European Region and in the United States of America, it is too early to draw any conclusions about the impact of Omicron will have on the global epidemiology of COVID-19.
Transmissibility
While there seems to be evidence that the Omicron variant may have a growth advantage over other circulating variants it is unknown whether this will translate into increased transmissibility. Based on several assumptions about the growth advantage, timing of introduction in the European Region, and population mixing and public health and social measures (PHSM) implementation, the European Centre for Disease Prevention and Control, forecasted that if 1% of SARS-CoV-2 infections are due to the Omicron variant, it will become dominant in Europe, comprising >50% of the new infections, by 1 January 2022, with a growth advantage of >120%; and by 1 March 2022 with a growth advantage of >30%.
Ongoing and planned epidemiological studies, including detailed cluster investigations, contact-tracing and household transmission studies, coupled with neutralization studies from people previously vaccinated or infected and studies of vaccine effectiveness will help improve our understanding of the interplay between increased transmissibility and immune escape as drivers of increased transmission.
Clinical severity
Currently only limited data are available, making it challenging to assess any changes in disease severity with the Omicron variant. As of 6 December, all of the 212 confirmed cases identified in 18 European Union countries for which there was information available on severity were asymptomatic or mild. While South Africa saw an 82% increase in hospital admissions due to COVID-19 (from 502 to 912) during the week 28 November – 4 December 2021, it is not yet known the proportion of these with the Omicron variant.5 Even if the severity is equal or potentially even lower than for Delta variant, it is expected that hospitalizations will increase if more people become infected and that there will be a time lag between an increase in the incidence of cases and an increase in the incidence of deaths. Further information is needed to fully understand the clinical picture of those infected with the Omicron variant and WHO encourages countries to contribute to the collection and sharing of hospitalized patient data through the WHO COVID-19 Clinical Data Platform.
Risk of reinfection
Preliminary analysis suggests that the mutations present in the Omicron variant may reduce neutralising activity of antibodies resulting in reduced protection from natural immunity. This may explain why the variant seems to be spreading rapidly in a highly immune population such as South Africa, in which current vaccination coverage in adults is about 35%, but in which seroprevalence levels are estimated to be as high as 60-80% due to past infections, according to recent epidemiological studies and modelling.
A modelling study (pre-print) based on data from nearly three million individuals in South Africa with a laboratory confirmed infection at least 90 days prior found an increase in the risk of re-infection during November 2021 compared to time periods earlier in the pandemic (estimated relative hazard ratio for reinfection versus primary infection of 2.39 (95%CI 1.88-3.11 from 1 – 27 November 2021 compared to wave 1 (June – September 2020), corresponding with the emergence of the Omicron variant. This information provides an initial assessment of the risk of re-infection however, further studies are needed to confirm this, including the ability of the Omicron variant to infect or re-infect those who have been vaccinated, as well as to determine the severity of these breakthrough or re-infections.
Impact on diagnostics
SARS-CoV-2 infection can be diagnosed using either molecular tests (NAAT, PCR) or antigen-detection assays. PCR tests that include multiple gene targets are unlikely to be affected and should continue to be used to detect SARS-CoV-2 infection, including the Omicron variant. This has been confirmed by statements issued by suppliers as well as the US FDA, based on sequence analysis.
The majority of Omicron variant sequences reported include a 69-70 deletion mutation in the Spike protein. There are some public sequences lacking this mutation and, at the present time, it is unclear if this reflects true sequence diversity or is a sequencing artifact. Presence of the 69-70 deletion causes dropout of some S-gene targets in PCR assays, such as the TaqPath COVID-19 Combo Kit and TaqPath COVID-19 CE-IVD RT-PCR Kit (Thermo Fisher Scientific). This S-gene target failure (SGTF) can be used as a marker suggestive of Omicron. However, confirmation should be performed by sequencing the sample, as this deletion is found in other VOCs (e.g., Alpha and subsets of Gamma and Delta) currently circulating at low levels globally, but possibly circulating at higher levels locally.
All four WHO emergency use listing (EUL) approved antigen-detection rapid diagnostic tests (Ag-RDTs), listed here, target the Nucleocapsid protein of SARS-COV-2.The vast majority of Omicron sequences reported to date include the G204R and R203K mutations in the Nucleocapsid protein, which are present in many other variants currently in circulation. This has not been reported to affect the accuracy of Ag-RDTs to detect SARS-CoV-2. In addition, the majority of Omicron sequences contain a 3 amino acid deletion at positions 31-33 and the P13L mutation in the Nucleocapsid protein. The specific impact of these mutations on the performance of Ag RDTs is currently unclear.
Official statements from several Ag-RDT suppliers, including two with EUL-approved assays, indicate that based on sequence analysis, the performance of their tests is not impacted by the Omicron variant. Preliminary laboratory evidence is emerging that independently confirms that Ag-RDTs can accurately diagnose infection with the Omicron variant. To date, there have been no reported misdiagnoses (false negative results) for any WHO EUL approved diagnostic product in relation to Omicron.
Impact on vaccines
There is a need for more data to assess whether the mutations present on the Omicron variant may result in reduced protection from vaccine derived immunity and data on vaccine effectiveness, including the use of additional vaccination doses. WHO will continue to work with partners to monitor and evaluate these data once they become available. Vaccine effectiveness studies are vital to understand how vaccines protect against infection, symptomatic and severe disease, and death.
Impact on treatments
WHO continues to work with researchers to understand the effectiveness of treatments against the Omicron variant; however, Interleukin-6 Receptor Blockers and corticosteroids are expected to continue to be effective in the management of patients with severe disease.
Conclusions
Whilst many questions about the Omicron variant remain unanswered, more information will continue to emerge in the coming weeks, with the TAG-VE and other groups reviewing and analysing data as it becomes available. It is important to continue to accelerate access to vaccines globally and for countries to continue to enhance surveillance, reporting initial cases or clusters to WHO and share genome sequences on publicly available databases such as GISAID. We recommend the public continue to prevent the spread of SARS-CoV-2 by improving ventilation of indoor spaces, wearing well-fitted masks, avoiding crowded spaces, practising hand hygiene and keeping an appropriate physical distance from others.
(Source:Weekly epidemiological update on COVID-19 – 7 December 2021.Edition 69)
