BA.2 sublineage with S:69/70del, S:E340K, S:K356T, S:L452R, S:R493Q, S:D936H (26 seq as of 2022-07-01, Ireland/various European countries/US)

[silcn]

Proposal for a sublineage of BA.2 Earliest sequence: 2022-05-02 (Ireland) Countries detected: Ireland (4 seq), Spain (1 seq)

Mutations on top of BA.2: S:69/70del, E340K, K356T, L452R, R493Q (reversion), D936H ORF1a:T3356I ORF3a:G100V E:L21F M:S4F (this is actually on a branch of BA.2+C22792T with over 160 sequences where 22792T has reverted back to C)

Sequences: EPI_ISL_12624715 EPI_ISL_13036609 EPI_ISL_13147723 (has additional S:L752F) EPI_ISL_13147735 EPI_ISL_13147550

This is another small lineage with lots of spike mutations that seems to be in general circulation, as it has been found in 4 different regions of Ireland as well as one sequence in Spain. There is some striking convergent evolution with BA.4/5. It seems fairly diverse too so there is presumably a lot more around than we're currently seeing.

The Usher tree is messed up by one sequence (EPI_ISL_12624715) with a dropout around S:452. In order to correct the tree I uploaded a fasta where I copied the dropout region from another sequence, but Usher still has the old EPI_ISL_12624715 without S:L452R, which you can ignore. S:D936H occurred before the other S mutations in a single sequence from New York. The rest all appeared together, including 69/70del which doesn't show up on Usher.

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_2dfe6_fdd680.json?branchLabel=Spike%20mutations&c=gt-S_340&label=nuc%20mutations:G24368C

[Sinickle]

Just a bit ago I did a review of all sequences with 3 of ([S:69-& S:70-], S:452X, S:486V, S:493Q) that aren't BA.4/BA.5 and had multiple sequences with circulation in May -- I believe there's only this branch and then one other branch.

So, the BA.4/BA.5 convergent evolution stands out quite a lot on its own.

In addition, mutations at S:340 are associated with Sotromivab resistance, and Bloom Lab claims that S:356 is likely a very heavily targeted site for immune response in folks who've had a breakthrough BA.1 infection.

[FedeGueli]

Great we are all on the same clusters of interests! @Sinickle was monitoring this as it was a couplet, same for you and Ryan and Sam and you for the other two .

[ryhisner]

With the E340K mutation, I suspect this is another sotrovimab-driven sublineage, many of which seem to also have S:D936H, though I don't know if there's any significance to that.

[silcn]

4 more sequences from Ireland, all sampled 2022-05-24: EPI_ISL_13178206 EPI_ISL_13186252 EPI_ISL_13186634 EPI_ISL_13186649

Usher tree is cleaner now as the 452-dropout sequence is showing as an erroneous reversion on the correct branch.

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_4134d_25cdb0.json?branchLabel=Spike%20mutations&c=userOrOld&label=nuc%20mutations:G22580A,A22629C,T22917G,G23040A,G25691T,C26533T

This lineage makes up 6 out of 243 sequences (2.5%) from week 21 in Ireland so far. Geographically it's spread all over Ireland. Too early to plot growth advantages of course, but for future reference here's a cov-spectrum query, allowing any mutation at S:340 because of the tendency for E -> K -> Q to happen:

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?variantQuery=S%3A340+%26+S%3A356T+%26+S%3A936H+%26+E%3AL21F+%26+M%3AS4F+%26+ORF3a%3AG100V&

[silcn]

Now also found in Florida: EPI_ISL_13225194, sampled 2022-05-18.

[chrisruis]

Will add a monitor label for now and see whether this expands in the coming weeks

[Sinickle]

Scotland now as well, with a 2022-06-10 sample date.

[corneliusroemer]

It's up to 11 sequences now. Really interesting lineage - because it mirrors so many of the BA.4/5 mutations and seems to have arisen independently (or through recombination?).

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?variantQuery=BA.2*+%26+S%3A356T+%26+S%3A936H&variantQuery1=BA.4*&pangoLineage2=BA.2*&

I'm strongly in favour of designation due to the very peculiar Spike mutation profile: Shared with BA.4/5 S:69/70del L452R R493Q (reversion)

Additional to BA.4/5 E340K K356T D936H

Missing with respect to BA.4/5 S:486V

This lineage has 9866T, so it's not unlikely it evolved outside of southern Africa (where 9866C is most common).

See here for comparison of mutations between BA.4, BA.2 and this lineage

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?variantQuery=BA.2*+%26+S%3A356T+%26+S%3A936H&variantQuery1=BA.4*&pangoLineage2=BA.2*&analysisMode=CompareEquals&

I'll remove the monitor label since I think it would be very good to have this designated for faster detection of more samples of this coming up. Also, it may be good if the origin of this lineage could be investigated as it parallels BA.4/5 so strongly. And a lineage designation is quite helpful to talk about it. It's also strongly associated with Ireland in terms of epidemiology.

[FedeGueli]

@corneliusroemer there is another sublineage that will be proposed soo by @josetteshoenma who did the analysis that shares with this one the 69/70 del and S:493Q reversion. Mentioning here cause maybe could be of some help to investigate the origins of these different lineages with some common features.

From #773 "Hi @silcn this morning i found a cluster in Germany with similar mutations (2 out of 8) S:R346K, S:H1101Y, S:460K, S:K147E) and the 493 reversion in Germany: EPI_ISL_13380484 EPI_ISL_13344896 EPI_ISL_13393217 EPI_ISL_13387937 EPI_ISL_13387015 EPI_ISL_13385893 EPI_ISL_13382835 EPI_ISL_13269776 EPI_ISL_13269123 EPI_ISL_13382561 EPI_ISL_13382506

"

[silcn]

Now found in England (EPI_ISL_13471163) and Czech Republic (EPI_ISL_13478306). Edit: and also one from Wales that is not on GISAID (Wales/PHWC-PJ7OY1/2022)

[silcn]

Newly found in Germany with an additional S:H49Y (EPI_ISL_13569569). 26 total sequences now.

[c19850727]

Just noticed that this cluster gained another NSP5 change: ORF1a:L3483F (NSP5:L220F) It's a bit unusual IMHO to have 3 changes in NSP5.

[ryhisner]

There's also a new sequence from England on the far right side of the tree, adding ORF3a:A39T and ORF1b:A1895T. Sequence collected on June 24.

[InfrPopGen]

Thanks for submitting. We've added lineage BA.2.77 with 13 newly designated sequences. Defining mutation(s) G22580A (S:E340K), A22629C (S:K356T), T22917G (S:L452R), G23040A (S:R493Q), G25691T (ORF3a:G100V), C26533T (M:S4F).

[FedeGueli]

39 seqs as today, steadily growing