Avian Flu Diary: UKHSA Initial Technical Briefing & Risk Assessment On COVID Omicron Variant (B.1.1.529)

COVID Sequencing In the UK

#16.384

While 99.8% of COVID cases in the UK sequenced in the UK between October 10th and Nov 30th are Delta (including sublineage AY.4.2 (VUI-21OCT-01)), all eyes are on the Omicron variant which has recent arrived in Europe, the United States and parts of Asia.

What it lacks in case numbers, Omicron more than makes up for in `red flags', including 30+ mutations in the spike protein which suggest it could not only be more transmissible, it may reduce currant vaccine and therapeutic effectiveness.

Many of these concerns are based on the large number of mutations in the RBD (Receptor Binding Domain) of the virus, and early reports of rapid spread in South Africa (see South African NICD Genomic Surveillance Report: Omicron 74% Of November Sequences). It will take a few weeks before we have good data to back that up, so for now the confidence level in the evidence remains low.

While it may not have any significant impact, much of the epidemiological data we have comes from South Africa, which is one of the few countries where the Beta variant spread widely in 2020 and early 2021.

As we saw in an earlier blog today (see Science: Heterologous Infection and Vaccination Shapes Immunity Against SARS-CoV-2 Variants), one's first exposure to a virus can determine their immune response to later infections.

Whether Beta's earlier appearance in South Africa affects their population's immune response to Omicron remains to be seen, but will be interesting to know.

Today the UK published a 40-page PDF:

Variant of concern: Omicron, VOC21NOV-01 (B.1.1.529)
Technical briefing 30

(Excerpt)
Summary

This specialist technical briefing contains early data and analysis on an emerging variant of concern Omicron VOC-21NOV-01 (B.1.1.529) and findings have a high level of uncertainty.

The data cut-off for this briefing is 30 November 2021 to allow for analyses. The most recent case numbers can be found here. The technical briefing will be updated weekly at present.

In summary:

• there are 5 current VOCs and 7 VUIs (Table 1). The World Health Organization (WHO) designated B.1.1.529 as a VOC, named Omicron, on 26 November 2021

• a new risk assessment for Omicron VOC-21NOV-01 (B.1.1.529) has been published

• Delta remains the predominant variant in England accounting for approximately 99.8% of sequenced cases from 10 October to 30 November 2021

• characterisation of the variant Omicron VOC-21NOV-01 (B.1.1.529) has commenced – a complete list of deployed and planned studies is provided in Section 2.1

• Omicron VOC-21NOV-01 (B.1.1.529) can be identified through genotyping or sequencing – as of 30 November 2021, there are 22 confirmed cases of Omicron VOC-21NOV-01 (B.1.1.529) identified through sequencing or genotyping in England; none of the cases of are known to have been hospitalised or died

• of the 22 confirmed cases, there are 12 cases who have received at least 2 doses of vaccine more than 14 days ago, 2 cases more than 28 days post first dose, 6 unvaccinated cases, and 2 with no available information

• the UKHSA genomic case definition for Omicron VOC-21NOV-01 (B.1.1.529) is included and has been published for use at GitHub

• Omicron VOC-21NOV-01 (B.1.1.529) can be detected through the current genotyping panel in use in England – the current profile requires K417N must be present, and P681R, E484K, and K417T must not be present; additional targets for Omicron VOC21NOV-01 (B.1.1.529) are being validated

• the Omicron VOC-21NOV-01 (B.1.1.529) global phylogeny shows little diversity which is compatible with a recent emergence and rapid spread – due to mixed sequence quality, requiring the masking of informative sites from the alignment, the phylogeny is not suitable for detailed cluster analysis, however it supports the epidemiological finding that there have been a number of separate introductions into England

• Omicron VOC-21NOV-01 (B.1.1.529) has a deletion at position 69/70 of the spike protein which allows it to be tracked through S gene target failure (SGTF) in some polymerase chain reaction (PCR) tests. SGTF is also observed in a very small fraction of test results from lineages lacking this deletion, including the Delta lineage and sub-lineages. The proportion of test results with SGTF has been low over the past 90 days, but in the past week has increased. The logistic growth rate of SGTF has fluctuated between approximately -50% and +50% over the past 90 days but in the past week has climbed to +141%. This finding indicates that SGTF is growing faster, and can be considered a strong early signal. However, the number cannot be interpreted as a change in transmissibility or an increase in the absolute number of cases of the variant.

• structural modelling shared by the University of Oxford indicates that the mutations present in Omicron are highly likely to affect the binding of natural and therapeutic antibodies, and to enhance binding to human Angiotensin-Converting Enzyme 2 (ACE2) to an extent greater than that seen in other variants to date. (Data not included; will be linked from here once available)

• there is very little evidence of Omicron VOC-21NOV-01 (B.1.1.529) in wastewater surveillance up to 21 November 2021; more recent data is being analysed

(Continue . . . )

The UKHSA has also published a risk analysis on the Omicron variant, based on the limited data available. I've posted the graphic, and reproduced the text, for easy reading. The big unknown remains the severity of infection, compared to other variants.

Transmissibility between humans
At least as transmissible as currently circulating variants Omicron is transmitting rapidly and successfully. Increased transmissibility compared to Delta is biologically plausible with the presence of furin cleavage site and nucleocapsid changes associated in vitro with advantages for replication, as well as extensive changes to the RBD. Structural modelling suggests that the mutations present may increase human ACE2 binding affinity to a much greater extent than that seen for any other variant. Phylogeny suggests a recent emergence. Data from South Africa suggests that Omicron has a pronounced growth advantage there. However, this may be due to transmissibility or immune escape related, or both.
Infection severity Insufficient data
Naturally acquired immunity
Mutations suggestive of reduced protection from natural immunity and limited supporting epidemiological evidence Based on experience with other variants, laboratory data on individual mutations, and structural modelling, the mutations present are very likely to reduce antibody binding and include changes in all 4 neutralising antibody binding sites in the RBD and also in antigenic sites in the S NTD. T cell epitope data is awaited. Analysis from South Africa suggests a reduction in protection from previous infection, including from recent Delta infection. There is no convalescent sera neutralisation data and no relative risk of reinfection analyses as yet
Vaccine-derived immunity
Mutations suggestive of reduced protection from vaccine derived immunity, no supporting evidence The mutations present are likely to reduce antibody binding and include changes in all 4 RBD neutralising antibody binding sites. T cell epitope data is awaited. There is no vaccinee sera neutralisation data and no epidemiological data on vaccine effectiveness
Therapeutics
Mutations suggestive of reduced effectiveness of a treatment in UK clinical use The mutations present are likely to reduce the binding of most available therapeutic monoclonal antibodies, based on structural modelling. On the same basis, they are unlikely to affect current small molecule antivirals. However, there is no laboratory or clinical data to support these predictions at present.