The XE recombinant contains BA.1 mutations for NSP1-6 and then BA.2 mutations for the remainder of the genome. As of 22 March 2022, there are 763 XE sequences in the UK data. As of 22 March 2022, there are 637 XE cases in England. These are geographically distributed across England and increasing in number, with the first case detected via sequencing on 19 January 2022, and most cases in East of England, London, and the South East.
The median growth rate is +9.8% per week.
Two new variants were identified as part of horizon scanning on 4 April 2022. Work is underway to precisely define the phylogeny of these variants. These have been designated as lineages BA.4 and BA.5 and classified by the VTG on 6 April 2022, as V-22APR-03 and V-22APR-04, respectively.
V-22APR-03 shares all mutations/deletions with the BA.2 lineage except the following: NSP4: L438F reverted to WT (wild type); S: 69/70 deletion, L452R, F486V, Q493 (WT); ORF 6: D61 (WT); ORF 7b: L11F; N: P151S. The spike 69/70 deletion will result in an undetectable S-gene target (S-gene target failure) in the Taqpath assay.
The earliest BA.4 sample in GISAID was from South Africa with a sample collection date of 10 January 2022. However, Figure 8 shows the accumulation of genomes and geographic spread is more recent. Countries reporting BA.4 genomes via GISAID now include South Africa (41 genomes), Denmark (3), Botswana (2) and England and Scotland reporting one each. Although the number of total genomes is small, the apparent geographic spread suggests that the variant is transmitting successfully.
BA.5 shares the same mutations/deletions as BA.4 except the following: M: D3N; ORF 7b: L11 (WT); N: P151 (WT); synonymous SNPs: A27038G, and C27889T.
Currently there are 27 sequences reported with this lineage, all from South Africa. This lineage shows sample dates between 25 February and 25 March 2022 (Figure 9).
Three different interpretations of 'end' to consider:
When is this going to end?
Three different interpretations of 'end' to consider:
In terms of the virus vanishing or becoming 100% irrelevant to public health, no end is expected. For example, even beyond the acute pandemic phase, we are to expect to have to manage seasonal waves of the virus and ongoing vaccination campaigns tied to expectations about those waves.
In terms of the acute phase of the pandemic and really heavy policies that have a large and obvious affect on everyones lives, we are already over a year into countries like the UK striving to get beyond that, with somewhat mixed results so far. If we ignore the ongoing deaths and health service pressures, then they have already 'succeeded', and we can also observe attitude changes on forums like this one which give the impression that a big chunk of that mission is already completed. However caveats remain, bringing me to the following description of third sort of 'end':
In terms of the rapid mutation of the virus in ways that keep heavier concerns on the table, potentially causing multiple waves per year which are not restricted to standard seasonal pattern assumptions, expectations still feature plenty of guesswork. The likes of Vallance a few months ago made it sound like the default assumption is that several more years of this are plausible before things might start to slow and settle. But there are many factors, and the implications of each new variant will vary. Countries also have some divergence in the timing and nature of their population immunity picture, which may in some cases have quite a large impact on the waves seen as a result of particular new variants.
It would certainly have been easier for me to declare an end to the acute phase of the pandemic if there had been a clear period where the mutation picture was more settled, resulting in a much larger gap between waves. Without that we have a messy situation where I can see why plenty of people think the acute phase of the pandemic is over, but where I cannot bring myself to draw the same conclusion. The vaccine era has made a big difference to the required policy responses, but has also enabled situations which ensure there are plenty of opportunities for the virus to continue its evolution at blistering speed, and with the impetus to do so.
Do you think that the very high risk/ very immunosuppressed will have to take their chances at some stage?
But sometimes I also get the feeling that there's some kind of avoidance of reality amongst many, who are unwilling to accept that things may not get much better than they are now.
That's not just because the picture has been changed by vaccination, but because the prospects of things getting very much better in the coming months or years don't look all that great.
For a start, lets examine when the moment of maximum 'as good as its going to get' was reached in your mind. Please do tell us when that was exactly.
Its not that easy to give a straightforward answer to that. The sort of answers I might be comfortable coming out with at this stage tend to wind some people up, they may moan that its a load of useless waffle. But thats just the nature of things at this stage, its a tug of war between viral evolution and the fact we arent talking about immune naive populations anymore, lots of immunity has built up via vaccination and prior infection.Yes, thanks. But what does all this mean in practical terms?
The MRC Biostatistics Unit (Cambridge) suggests that, for England, the current wave will peak in the week 17th-23rd July.There might be hints of BA.5.x beginning to falter, as it increasingly struggles to find sufficient susceptibles over the coming fortnight.
DOI:10.1101/2022.07.12.499603.Here, we demonstrate that the most recent Omicron variants have enhanced capacity to antagonise or evade human innate immune defenses. We find Omicron BA.4 and BA.5 replication is associated with reduced activation of epithelial innate immune responses versus earlier BA.1 and BA.2 subvariants. We also find enhanced expression of innate immune antagonist proteins Orf6 and N, similar to Alpha, suggesting common pathways of human adaptation and linking VOC dominance to improved innate immune evasion. We conclude that Omicron BA.4 and BA.5 have combined evolution of antibody escape with enhanced antagonism of human innate immunity to improve transmission and possibly reduce immune protection from severe disease.
Add BA.2.75.1 (defining mutation S: D574V) to that list. It might start driving an autumnal wave earlier (second half of September).