BE.1.1.1 sublineage with Orf1b:Y264H and S:N460K ( 69 sequences ) emerged in Nigeria ( 14 seqs )

[FedeGueli]

Detected a new potential sublineage of interest of recently designated BE.1.1.1.
Defining mutations : Orf1b:Y264H and S:N460K
7 sequences Usa Uk Japan
The one from Japan (EPI_ISL_14632425 )
was intercepted by airport surveillance and has travel history from Egypt via Italy and Israel to Japan and it is heavily mutated with further spike mutations: S:261D*,S:494P and S:603S.
(* as noted by @ryhisner elsewhere S:G261D is or highly homoplasic mutation or pipeline artifact , it was present in a lot of samples from Japanese airport surveillance yesterday maybe Ryan could explain that better than me.)
This could suggest circulation and evolution in an undersampled area of Africa likely , due to the fact that the likely origin of BE.1.1.1 lineage is Nigeria)

Gisaid query: NSP12_Y273H,Spike_K444T,Spike_N460K finds 6 out of 7
CovSpectrum: 4 out of 7 Overview

tree: https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_3ba8a_876050.json?c=pango_lineage_usher&label=nuc%20mutations:T14257C

List of sequences:

EPI_ISL_14294806
EPI_ISL_14333750
EPI_ISL_14333754
EPI_ISL_14542445
EPI_ISL_14608324
EPI_ISL_14632425
England/PHEC-YYGIB6T/2022|2022-08-12

Originally posted by @FedeGueli in #931 (comment)

I decided to open an issue after just 7 sequences for three reason:
1-Convergent evolution at S:460 with BA.2.75
2-Already Sampled in 4 continents suggesting high or growing prevalence somewhere likely in Africa
3-BE.1.1.1 is the fastest BA.5 sublineage according to our collection on covspectrum :

https://cov-spectrum.org/collections/24
:

[cvejris]

I concur that early attention is in place here. The affinity impact of S:N460K is huge, see https://www.biorxiv.org/content/10.1101/2022.08.07.503115v1.full and https://www.biorxiv.org/content/10.1101/2022.07.18.500332v2.full
I would also worry about Orf1b:Y264H. Mutations before position 700 in Orf1b (NSP12; RNA polymerase) are extremely rare among VOC, see https://outbreak.info/compare-lineages?pango=Alpha&pango=Beta&pango=Gamma&pango=Delta&pango=Epsilon&pango=Mu&pango=Iota&pango=Kappa&pango=Lambda&pango=Theta&gene=ORF1b&threshold=75&nthresh=1&sub=false&dark=false
The handful present apparently pose selective advantage, see https://www.biorxiv.org/content/10.1101/2022.01.07.475295v1.full These are P314L (defining for B.1) and G662S (defining for delta, 3x independently in BA.2: BA.2.75, BA.2.10.4 and BJ.1).

[ryhisner]

It's possible part of the reason BA.2.75 has been able to pick up immune-evasive mutations so much more quickly than BA.5 is because of its higher ACE2 affinity, mostly due to S:N460K. If N460K has a similar effect in BE.1.1.1, it could allow it to acquire still more mutations to evade vaccine- and infection-induced immunity, a factor which will only increase in importance as more and more people are infected with BA.4/5 and/or vaccinated with BA.1- or BA.5-based vaccines. Given that this one is already widespread geographically—possibly far more than we can currently tell—I think it bears close monitoring and probably a rapid designation if more sequences continue to appear in the next week or two.

[Mydtlwn]

I'm not very good at using this, so I don't know the meaning of this corresponding time.

[corneliusroemer]

@Mydtlwn If you mean the early first date - this is just a normal date error. Happens all the time - probably would be best to scrape that "first date" column from cov-lineages website for that reason or make it more robust (e.g. date of 1% quantile)

[FedeGueli]

I concur that early attention is in place here. The affinity impact of S:N460K is huge, see https://www.biorxiv.org/content/10.1101/2022.08.07.503115v1.full and https://www.biorxiv.org/content/10.1101/2022.07.18.500332v2.full I would also worry about Orf1b:Y264H. Mutations before position 700 in Orf1b (NSP12; RNA polymerase) are extremely rare among VOC, see https://outbreak.info/compare-lineages?pango=Alpha&pango=Beta&pango=Gamma&pango=Delta&pango=Epsilon&pango=Mu&pango=Iota&pango=Kappa&pango=Lambda&pango=Theta&gene=ORF1b&threshold=75&nthresh=1&sub=false&dark=false The handful present apparently pose selective advantage, see https://www.biorxiv.org/content/10.1101/2022.01.07.475295v1.full These are P314L (defining for B.1) and G662S (defining for delta, 3x independently in BA.2: BA.2.75, BA.2.10.4 and BJ.1).

There was ORF1b:K82R in the sibling lineage of Ay.103 that was only partially designated as AY.41 (I opened an issue back months ago) that opened breaches in eastern (balcanic) Europe

#440

[FedeGueli]

New sequence from Georgia state - US collected 8/08/22 : EPI_ISL_14675347 with an additional Orf9b:R13L, Orf1a:A2856V
ORF7a:T120I mutations
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_1d7b4_a0ee60.json?label=nuc%20mutations:T14257C

[FedeGueli]

New sequence from Germany : EPI_ISL_14697838 (this last has one more spike mutation: S:I666V)

[FedeGueli]

3 more sequences from Nigeria (where it likely emerged)

EPI_ISL_14711977
EPI_ISL_14711975
EPI_ISL_14711972

all collected on 10th of July.

I suggest flagging this sublineage to health authorities , it could be really a step beyond BA.5. cc @corneliusroemer @chrisruis @InfrPopGen

EDITED
Digging a bit more i saw that there were 16 samples uploaded today of BE.1.1 + orf1b:Y264H (
13 of them have unknown aminoacid X at Spike resiudes 444-460 .
I am quite confident that most or all of them have both 444T and 460K.

List of sequences from Nigeria:
EPI_ISL_14711952
EPI_ISL_14711964
EPI_ISL_14711966
EPI_ISL_14711970
EPI_ISL_14711971
EPI_ISL_14711972 (confirmed)
EPI_ISL_14711973
EPI_ISL_14711974
EPI_ISL_14711975 (confirmed)
EPI_ISL_14711976
EPI_ISL_14711977 (confirmed)
EPI_ISL_14711978
EPI_ISL_14711982
EPI_ISL_14711985
EPI_ISL_14711986
EPI_ISL_14711987

[FedeGueli]

New Usher tree for the new sequences from Nigeria ( @AngieHinrichs ) confirms at least 14 out of 16 sequences are part of this new sublineage:

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_3f237_d48520.json?label=nuc%20mutations:T14257C

New things on the table:
10 out of 14 sequences from Nigeria cluster together sharing an additional orf1b mutation: Orf1b:N1191S
1 out of 14 sequences from Nigeria has S:I666V as the other sequence uploaded today from Germany

the two sequence that Usher doesnt place in the S:N460K cluster, one (hCoV-19/Nigeria/NCDC-NR-GL-005829/2022|EPI_ISL_14711966|2022-07-10) is clearly linked and could be considered basal to this new lineage together with a sequence from Usa (USA/DC-Curative-451803/2022|EPI_ISL_14464964|2022-08-06) that has too X aminoacid in the region spanning Spike residues 444-460 so it could be instead part of it.

((while the other one (hCoV-19/Nigeria/NCDC-NR-GL-005827/2022|EPI_ISL_14711964|2022-07-10) is placed in a messy BA.5.5/Ba.5.3 part of the tree: https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice2_genome_3f237_d48520.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:C11750T))

[FedeGueli]

One more sequence from France : EPI_ISL_14726834 collected on 8/8/22
this one has S:54F and N:334I
and it clusters with USA/GA-GPHL-2435/2022|OP208252.1|2022-07-29

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_2f2c_e25c50.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:T14257C

To me such a diversity suggests sustained circulation likely in the region where it emerged first.

[corneliusroemer]

If we get a few more this should be designated as there's quite some literature on 460K if I'm not mistaken

[FedeGueli]

@corneliusroemer two more sequences from Texas uploaded today and collected 7/08 and 21/08:

EPI_ISL_14752457
EPI_ISL_14753714

[FedeGueli]

New Usher tree generated:https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_285be_f8f870.json?branchLabel=aa%20mutations&label=nuc%20mutations:T14257C

[FedeGueli]

Oh bad news EPI_ISL_14752457 the recent Texas sequence got S:346T @corneliusroemer

[FedeGueli]

New sequence new country: Belgium EPI_ISL_14773615 collected on 24/08/2022

[FedeGueli]

One more sequence from Oregon, Usa: EPI_ISL_14777488

[corneliusroemer]

@FedeGueli feel free to propose the most "promising" lineages in your view, the 346T sound interesting, definitely something to monitor and designate once it gets above 5 or maybe 10.

[FedeGueli]

4 more sequences: Denmark, Rhode Island , Georgia and Canada (intl Airport surveillance from unknown country).
No one with S:R346T luckily. One with S:L54F

I noticed that the belgian one i highlighted above beyond S:346T has a reversion at 484 to E that i missed before.

Ok @corneliusroemer i ll wait a bit to have a more clear picture and then i will propose sublineages of it.

[FedeGueli]

4 new seqs from Denmark, Uk and 2 from Germany one of them with S:R346T.

Later i ll.propose the S:346T sublineage.
@corneliusroemer

[corneliusroemer]

I'll designate the S:R346T straightaway, seeing how fast BQ.1 grows and that the 5 S:R346T are from 5 countries and very recent.

[corneliusroemer]

Here's an Usher tree with all sequences (some are duplicated because I uploaded all 66 that the GISAID query found, and they were partially in the tree already):

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_8362_b889b0.json?branchLabel=aa%20mutations&label=nuc%20mutations:T22942A

[corneliusroemer]

I've added BQ.1.1 on the ORF1b:N1191S branch defined by S:R346T in commit 44c66bc

Thanks @FedeGueli

[FedeGueli]

Thanks @corneliusroemer great work!

[FedeGueli]

Gisaid query for BQ.1.1:Gisaid: Spike_N460K,Spike_K444T,Spike_R346T,Nsp13_N268S

[FedeGueli]

Already 7 BQ.1.1 (two newly uploaded and one of them sampled in Japan coming from Nigeria as noted by @ryhisner .) beyond these two there were 9 BQ.1 uploaded 8 from Usa and 1 from Greece .
total count 69 BQ.1 of which 7 BQ.1.1

[corneliusroemer]

There are now 12 BQ.1.1 already

[FedeGueli]

11 BQ.1.1 uploaded yesterday mostly England, and 2 new countries Belgium and Italy.
3 new samples today from England.
There are already 32 BQ.1.1 viruses on Gisaid.

@corneliusroemer @thomaspeacock it seems really fast.

[FedeGueli]

2 danish BQ.1 sequences with a couple of spike mutations: Spike_R190T,Spike_N556K.

@ryhisner apotteda couple of BQ.1 with S:T444M T > M that is to be monitored. I suggest to use this modified query: NSP12_Y273H,Spike_K444,Spike_N460K

[FedeGueli]

one more sequence of BQ.1 with S:_R190T but without S:N556K.

Total counts as today:
BQ.1 = 152 seqs
BQ.1.1 = 41 (with new query suggested by @josetteshoenma : NSP12_Y273H,Spike_R346T,Nsp13_N268S)

[FedeGueli]

8 BQ.1.1 from.Uk uploaded today all with S:L822F mutation.
It could be a cluster as usual happens in Uk and Denmark .
But i will monitor it closely.
@corneliusroemer @thomaspeacock @InfrPopGen

[FedeGueli]

From #931:

Something we all missed and partially just @Sinickle noticed in #931 is that the nuc mutation C28312T in BE.1.1.1 together with 28311T (ORF9b:P10S) common to all Omicron sublineages gives an AA mutation Orf9b:P10F

BQ.1.1 From WT BQ.1.1 from BA.2

cc @corneliusroemer @AngieHinrichs @InfrPopGen @chrisruis @thomaspeacock It wasn't maybe so relevant until a potential dominant lineage as BQ.1.1 emerged from this root

[cvejris]

I realized this just today by looking at Venn diagram by @RajLABN https://twitter.com/RajlabN/status/1572480532478320642/photo/1

[carlottaolivero]

We don't know if it is relevant of note, but we have noticed that for:
BA.2.75 and subvariants, S:N460K derivates from T22942G
whereas
BQ.1 and subvariants, S:N460K derivates from T22942A

[FedeGueli]

@carlottaolivero thx! great catch! i did a rapid query on covspectrum i found that T22942A is in BQ.1* , XAW and some of the BA.5.2 +460K we saw in the last times.
While T22942G is in BA.2.75*(all lineages), BA.2.3.20, BS.1, BU.1, XBB, XAK and BW.1 (BA.5.6.2.1)

[icestorm972]

FYI @corneliusroemer

In Germany's RKI DESH DATA are now (since 2022-08-15 / KW33):

• 38 BE.1.1.1 with S:K444T but without S:N460K
• 32 BQ.1(.*) with S:K444T and S:N460K

Proportion

Absolute

[fiuzatayna]

Outbreak Info and Cov-lineages list BQ.1.1 first sequence as showing up in October 15... 2020. Isn't it a mistake? Where does it come from... Could it be from faulty metadata on gisaid?

Upon inspecting GISAID, it even flags the "2020" sequence as an outlier, as its collection date is earlier than the clade name submission. Shouldn't outbreak info and cov-lineages filter such sequences out?

Thank you for clarifying.

[AngieHinrichs]

Could it be from faulty metadata on gisaid?

Most likely yes. If you have time to contact the submitters, sometimes they are responsive and fix the record, sometimes not. Another thing that can happen is that they pull an old sample out of the freezer (so the collection date is true) -- but then contamination happens during sequencing.

[fiuzatayna]

I'll try to contact them and I'll let you know if anything changes.

Could it be from faulty metadata on gisaid?

Most likely yes. If you have time to contact the submitters, sometimes they are responsive and fix the record, sometimes not. Another thing that can happen is that they pull an old sample out of the freezer (so the collection date is true) -- but then contamination happens during sequencing.