CH.1.1 sublineage with S:P681R in Austria and Germany (58 sequences)

[BorisUitham]

CH.1.1 sublineage with S:P681R in Austria, Germany (25 sequences)

Description: Sub-lineage of CH.1.1 with S:P681R
Earliest sequence: 2022-11-02
Most recent sequence: 2022-11-30
Countries circulating: Austria (33 sequences), Germany (1 sequence)
GISAID query: Spike_P681R, Spike_G339H, Spike_R346T, Spike_L452R

34 sequences of this CH.1.1 with the S:P681R mutation that is found in Delta, which is thought to be responsible for increased fusogenicity and pathogenicity. 33 sequences are from Vorarlberg, Austria and 1 from Baden-Wurttemberg, Germany.

Genomes
EPI_ISL_15915257
EPI_ISL_15915215
EPI_ISL_15915238
EPI_ISL_15915220
EPI_ISL_15915143
EPI_ISL_15915165
EPI_ISL_15916122
EPI_ISL_15816173
EPI_ISL_15816096
EPI_ISL_15816063
EPI_ISL_15747319
EPI_ISL_15747592

Evidence
USHER is unable to build a phylogenetic tree, since in the Austrian samples only a part of the spike was sequenced.

Nextclade:

All Austrian samples containing a P681R mutation in Austria in October and November. Overview provided by @JosetteSchoenma

Covspectrum query:
https://cov-spectrum.org/explore/World/AllSamples/Past3M/variants?aaMutations=S%3AP681R&nextcladePangoLineage=CH.1.1*&

Growth advantage:
Too early to tell, however parent lineage CH.1.1 has a growth advantage thought to be around the same as BQ.1.1, and there are already 25 sequences in its first month of detection.

Sidenotes:
Interestingly, there seems to be a BF.7.9 (EPI_ISL_15816454 on 2022-11-08) and an AY.78 (EPI_ISL_15746291 on 2022-10-31) with the S:P681R mutation found in the same time period, also in Austria. It could be possible that this lineage is a recombinant with the BF.7.9 sublineage. Once a sample has been fully sequenced, it is interesting to look for 969K and 954H mutations, which are implicated in the altered cell entry phenotype of Omicron.

Thanks to @JosetteSchoenma for helping with putting the proposal together.
Also found by @health_enjoyer on twitter on november 22nd.

[JosetteSchoenma]

Well done, @BorisUitham . Your first proposal!
Hopefully there will be a fully sequenced sample available soon. Among other things, to see if this is a recombinant or just a mutated CH.1.1.

[FedeGueli]

congrats great catch and great 1st proposal also @ryhisner and @UlrichElling are on these sequences

[UlrichElling]

Thanks everyone! Full genome sequencing ongoing.

[thomasppeacock]

Putting a monitor label on until we have full genomes and therefore get some more complete tree placement, etc

[corneliusroemer]

All 12 sequences are from Vorarlberg, Austria

Do you know anything more about whether the patients are related? All being from one place this doesn't reall

with the S:P681R mutation that is found in Delta, which is thought to be responsible for increased fusogenicity, pathogenicity and transmission

I would take increased transmission claims with a big grain of salt. If this mutation was beneficial in a BA.2/4/5/75 background it would have arisen much more often than the ~100 sequences we find on GISAID.

In BA.5 it hasn't done anything at all.

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?nextcladePangoLineage=BA.5*&aaMutations1=S%3A681R&nextcladePangoLineage1=BA.5*&analysisMode=CompareToBaseline&

[JosetteSchoenma]

Well, there is no metadata on GISAID, but the Sampling Strategy says 'random'.
Maybe @UlrichElling knows more?

In Vorarlberg it seems to grow, but of course the numbers are still very small. 2/186 in week 44, 4/199 in week 45 and 6/183 in week 46.

[UlrichElling]

I have no access to detailed metadata nor to cluster relationships. I can request it but do not expect a return of detailed information. As for growth I agree with Cornelius: I believe it is most likely a founder effect as the mutation has appeared early it seems in CH.1.1 and CH.1.1 itself is expanding. We have no evidence at this point that P681R would make CH.1.1 faster.

[BorisUitham]

I included the "increased transmission" based on a delta-era paper where this mutation is connected with increased viral replication (https://pubmed.ncbi.nlm.nih.gov/34462752/) when compared to a delta without p681r. But in hindsight this indeed shouldn't be extrapolated to omicron and doesnt directly say something about transmission anyways, so i'll remove that part of the proposal

[Mydtlwn]

I think this can be observed for a while.

[FedeGueli]

Spike_P681R,Spike_G339H,Spike_R346T,Spike_L452R avoid to catch a CA.3 that popped up from india with 681R today

[FedeGueli]

19 sequences so 7 new ones uploaded from Austria today. @JosetteSchoenma @UlrichElling

[JosetteSchoenma]

Thanks, Fede. Just saw them. All from Vorarlberg again. And Spike only sequences.
It's now 1,1%, 2,0%, 3,4% and 2,4% from weeks 44 to 47. Based on around 200 samples in total per week.

[corneliusroemer]

@UlrichElling any progress on full genomes? Would be great to get these.

Also, could you maybe share the raw reads of the sequences in question? Would be good to see how clean they are to exclude contamination etc.

They all have an N-stretch at 22064-22222, so this could indicate an artefact.

It's suspicious that we've only seen these sequences from one Austrian state and not any neighbouring countries. I would suspect Labor Risch would have picked up on these in Liechtenstein etc, they upsample SGTP which these samples seem to be.