#16,316
Although the rest of the world is pretty much just watching and waiting, 3 weeks ago the UK - which is currently reporting the highest incidence of the AY.4.2 Delta sublineage - elevated this emerging variant to a VUI (Variant Under Investigation).
At that time, this descendent of the dominant Delta B.1.617.2 reportedly accounted for about 6% of the cases in the UK.
The latest report from the UK Health Security Agency (SARS-CoV-2 variants of concern and variants under investigation in England - Technical Briefing 28) includes the following points in its summary:
- Delta remains the predominant variant accounting for approximately 99.8% of sequenced cases in England from 10 October to 8 November 2021.
- The Delta sublineage AY.4.2 (VUI-21OCT-01) accounts for a slowly increasing proportion of cases in the UK. It accounts for 11.2% of Delta cases in the most recent complete week of sequencing (17 October 2021 to 23 October 2021). In more recent weeks, sequencing data is incomplete, however AY.4.2 accounts for 13.0% of Delta cases in the week 24 October 2021 to 30 October 2021 and 14.7% in the week 31 October 2021 to 6 November 2021.
- Vaccine effectiveness analysis does not suggest a significant reduction in vaccine effectiveness for AY.4.2 compared to other Delta viruses. Analysis using the standard test negative case control study does not indicate reduction in vaccine effectiveness for AY.4.2 as compared to non AY.4.2.
- Preliminary viral neutralisation studies with post-vaccination sera against AY.4.2 virus shows a 2.8 fold drop in comparison the wild-type virus, similar to Delta which showed a 3.2 fold drop in neutralisation (Genotype to Phenotype consortium)
Under transmissibility between humans, which is the greatest concern right now, they write:
AY.4.2. continues to increase in prevalence slowly in England. There is an increased growth rate for AY.4.2. compared to other circulating variants in 2 separate models, and this is now consistent across regions of England. There is a small increase in secondary attack rate and in household transmission risk, though both these analyses have limitations as they are derived from routine testing and tracing data systems. There is also a slowly increasing prevalence and an increased growth rate for AY.4.2 in incoming travellers to the UK. However, there is as yet no other country reporting the same effect through domestic surveillance and there is some conflicting evidence from community survey data. Confidence in this finding therefore remains low.
For now, AY.4.2 is most prevalent in the UK (as was Alpha, before it began its world tour), but the UK's Technical Briefing 28 (52-pages) lists more then 3 dozens countries that have reported this emerging subvariant.
International epidemiology
As of 8 November 2021, 2,072 sequences on GISAID meet the VUI-21OCT-01 definition from 41 countries excluding the UK (Figure 10), with 2,041 having suitable dates. The case definition has not been validated on international data and will be further assessed; results are provisional.
Using the surveillance case definition. sequences are identified from Germany (493), Denmark (413), Poland (203), United States (128), Italy (117), Ireland (96), Belgium (95), Romania (79), France (68), Spain (55), Switzerland (53), Netherlands (49), India (24), Norway (24), Bulgaria (16), Slovakia (14), Canada (13), Czechia (11), Portugal (10), Lithuania (10) and 21 other countries with fewer than 10 sequences.Using the surveillance case definition. sequences are identified from Germany (493), Denmark (413), Poland (203), United States (128), Italy (117), Ireland (96), Belgium (95), Romania (79), France (68), Spain (55), Switzerland (53), Netherlands (49), India (24), Norway (24), Bulgaria (16), Slovakia (14), Canada (13), Czechia (11), Portugal (10), Lithuania (10) and 21 other countries with fewer than 10 sequences.
Sequences shown before late June 2021 in meet the VUI-21OCT-01 definition, but do not have an amino acid call at the site 145, and therefore could either be wildtype or mutant. Using a stricter definition requiring all 3 mutations from the VUI-21OCT-01 definition results in 1,593 sequences present on GISAID as of 8 November 2021, from 35 countries.
While not nearly as common as AY.4.2, the Delta B.1.617.2 with the E484K mutation, due to its apparent neutralisation resistance, is also getting a good deal of attention. It was singled out in Wednesday's study out of Denmark as worthy of enhanced surveillance, and is also featured prominently (along with E484Q) in the UK's latest report.
Delta with E484K was first detected on 8 July 2021 in a UK sequence with a collection date of 28 June 2021. As of 8 November 2021, 152 sequences have been identified with 141 from England, 8 from Scotland and 3 from Wales, an increase of 59 since the briefing of 15 October 2021. The prevalence of this mutation is 0.02% of all Delta genomes in the UK and 0.07% of Delta sequences (where the mutation could be called) for the week beginning 18 October 2021, which is the last complete week of sequencing data. Internationally, as of 08 November 2021 the prevalence of Delta with E484K mutations is 0.03% of Delta genomes on GISAID (including the UK).
Epidemiology in England
As of 8 November 2021, there are 152 Delta with E484K sequences, a subset of which have been identified as belonging to 3 separate clusters. Cluster 1 contains 12 sequences, cluster 2 contains 87 sequences and cluster 3 contains 21 sequences in the UK. Of the 87 Delta with E484K sequences in in cluster 2 the UK, 70 could be linked to epidemiological data in England. Cases have been detected across 7 English regions, with most cases in the North West (57, 81.4%) as shown by region in Table 6, Figure 19 and by age in Figure 20. Of the 70 cases, 9 have history of travel.
So far, Delta with E484x mutations make up an extremely small percentage of cases in the UK, and show little sign of being able to compete with Delta or AY.4.2.
While AY.4.2 is making an impressive run against the dominant Delta virus in the UK, thus far, we haven't seen it making any significant inroads outside of Great Britain. It is unclear how much of a factor - if any - it is playing in the recent COVID surges in Eastern Europe and Russia.
It does, however, bear watching.
Because Delta, as firmly entrenched as it currently is, will likely give up its dominance to another variant at some point down the road. And right now, AY.4.2 is a likely contender.
