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Repository for suggesting new lineages that should be added to the current scheme
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New fast growing Delta sublineage with 4 distinct Spike mutations observed in multiple European countries #215

Closed corneliusroemer closed 3 years ago

corneliusroemer commented 3 years ago

Proposal for new sublineage within B.1.617.2 by Cornelius Roemer and @Chaoran-Chen

Defining AA mutations Occurred first: S:29A, S:250I Followed by: S:T299I Last (defining): S:Q613H

First observation 2021-06-11 in Japan Inferred common ancestor using time tree: April-June 2021

Latest sequence 2021-09-07

Countries Observed in 25 countries, mostly in Belgium, Denmark, France, Netherlands, Germany

image https://nextstrain.org/groups/neherlab/ncov/belgium?c=gt-S_299,613

Description Examination of the latest neherlab/Europe Nextstrain build showed a distinct lineage with 4 new spike mutations (S:29A, S:250I, S:299I, S:613H) on top of the Delta spike mutations. Further investigation using cov-spectrum showed that the lineage is widespread in Europe, in particular in France, Belgium and the Netherlands and is growing fast in proportion. In many countries examined, the growth advantage seems to be on the order of 10-40%. The proportion of sequences belonging to this lineage seem to reach already 1-10% in some countries. The number of spike mutations is indicative of a monophyletic origin.

The first few sequences on GISAID with these 4 mutations were obtained here:

strain date region_original country_original division Ns
hCoV-19/Japan/IC-1357/2021 2021-06-11 Asia Japan   0
hCoV-19/Morocco/RA207/2021 2021-06-20 Africa Morocco   0
hCoV-19/Israel/SMC-7005096/2021 2021-06-28 Asia Israel   180
hCoV-19/Netherlands/GR-RIVM-47410/2021 2021-06-30 Europe Netherlands Groningen 0
hCoV-19/Belgium/UZA-UA-47848402/2021 2021-07-03 Europe Belgium Antwerpen 0
hCoV-19/Germany/NI-RKI-I-187479/2021 2021-07-04 Europe Germany Niedersachsen 124
hCoV-19/Northern Ireland/PHEC-M30AM407/2021 2021-07-05 Europe United Kingdom Northern Ireland 0
hCoV-19/Belgium/UZA-UA-CV2253887754/2021 2021-07-06 Europe Belgium Antwerpen 3
hCoV-19/France/PDL-IPP15314/2021 2021-07-06 Europe France Pays de La Loire 475
hCoV-19/France/IDF-HMN-21072080322/2021 2021-07-06 Europe France Ile de France 248
hCoV-19/France/GES-HMN-21072120416/2021 2021-07-07 Europe France Grand Est 392
hCoV-19/France/BFC-HMN-21072220511/2021 2021-07-07 Europe France Bourgogne-France-Comté 254
hCoV-19/Canada/QC-L00365546001/2021 2021-07-08 North America Canada Quebec 571
hCoV-19/ITA/ABR-A39164/2021 2021-07-09 Europe Italy Abruzzo 0

The lineage has been observed in a significant number of countries (Morocco, Belgium, Switzerland, Netherlands).

The second earliest sequences is from Morocco and Morocco does not sequence much at all (only a dozen in the last few months). Together with the fact that the lineage suddenly appeared in multiple European countries that have historically close ties with Morocco (France, Belgium, Netherlands) makes it quite plausible to me that this lineage was exported from Morocco.

Country Sequence count
Belgium 482
Denmark 266
France 255
Germany 213
United Kingdom 106
Netherlands 89
USA 86
Italy 60
Switzerland 49
Spain 42
Sweden 28
Austria 8
Canada 6
Norway 3
South Korea 3
Finland 2
Ireland 2
Israel 2
Japan 2
Hong Kong 1
Iceland 1
Morocco 1
Portugal 1
Romania 1
Singapore 1

Strains: strains.csv

Screenshots: image https://nextstrain.org/groups/neherlab/ncov/europe/2021-09-09?branchLabel=aa&c=gt-S_29,250,299,613&gmin=15&m=div

Growth in share in all European sequences: image https://cov-spectrum.ethz.ch/explore/Europe/AllSamples/AllTimes/variants/json=%7B%22variant%22%3A%7B%22mutations%22%3A[%22S%3A29A%22%2C%22S%3A250I%22%2C%22S%3A299I%22%2C%22S%3A613H%22]%7D%2C%22matchPercentage%22%3A1%7D

And the corresponding data as a table (note in the table the proportion is of Delta whereas in the graph it's proportion of all sequences):

year week delta_count (Europe) new_lineage_count (Europe) proportion of lineage of all Delta (Europe)
2021 26 9509 3 0.03%
2021 27 15930 13 0.08%
2021 28 17237 24 0.14%
2021 29 22934 54 0.24%
2021 30 23008 103 0.45%
2021 31 22082 195 0.88%
2021 32 28400 306 1.08%
2021 33 36941 307 0.83%
2021 34 14781 225 1.52%
2021 35 5344 121 2.26%
2021 36 58 1 1.72%

This is Usher with the selected strain names image

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/singleSubtreeAuspice_genome_5e61a_b90a90.json?branchLabel=Spike%20mutations

chaoran-chen commented 3 years ago

This shows the prevalence of the four mutations among delta sequences in different countries.

prevalence_within_delta

c19850727 commented 3 years ago

looks like the same one as #206 (proposed new lineage 4) ?

FedeGueli commented 3 years ago

Yes it is the same one as lineage 4 proposed in #206 , probably it needs a second chance to be designated.

rmcolq commented 3 years ago

I'm looking into designating it now

corneliusroemer commented 3 years ago

Closed in https://github.com/cov-lineages/pango-designation/commit/4ba575250d207bb528693ba9250f8c35e31739d7

corneliusroemer commented 3 years ago

@rmcolq Thanks for designating so quickly! I closed it because you've designated it, but it probably should still get the designated label.

shay671 commented 3 years ago

One of the interesting thing is how a variant is spreading in correlation to it's most closest branch. In case of AY.33 this is the clade described as clade D (ref in the end of this message), the clade which included N_G215C (among other 12 mutations over the base of Delta and 9 over a base of 4 out of the 5 Delta clades) and which is the one taking over the world. AY.33 has 4 mutations over Delta clade D (all in S1 as mentioned).

I took from GISAID the samples of Delta D from 3 countries in which AY.33 is spreading and also the AY.33 samples. Delta D was taken using the mutation signature : Spike_L452R,Spike_P681R,N_G215C Ay.33 was taken using the mutations signature : Spike_L452R,Spike_P681R,N_G215C,S_T299I,S_Q613H image

image

image

It is important to mention - In the past i did this analysis of other Delta D based AY variants such as AY.1,AY.3,AY.4 and no such increase was found. But this trend is seen in several countries with AY.23

The paper were Delta D and it's kinetics was shown : https://www.medrxiv.org/content/10.1101/2021.08.05.21261642v1

shay671 commented 3 years ago

The reason for this analysis is as seen with AY.1,AY.3 and AY.4 - this trend may be just the regular increase of Delta D over all the other 4 clades of Delta (meaning that it may be just a reporter for Delta D) which is still occur in many countries.

silcn commented 3 years ago

A lineage going quickly up to ~10% and then getting stuck there (Belgium) seems more likely due to lots of introductions in a relatively short period rather than an increase in fitness. For all we know, AY.33 could be dominant in Morocco, and I note that Belgium has a particularly large Moroccan diaspora so there was probably a lot of travel between the two countries over the summer holidays. Germany and the UK appear to show a similar effect - I wouldn't read much into the figures from the latest week where sequencing is clearly far from complete.

Denmark does not have a large North African population so possible that introductions there would be later on average, as they would tend to come from other European countries rather than Africa.

AY.33 still might have an advantage but surely it would have to be small. This reminds me more of Kappa vs Alpha in the UK than Delta vs Alpha.

corneliusroemer commented 3 years ago

@rmcolq @chrisruis

I've looked at the data around this lineage AY.33 more closely and it may be worth to designate a parent of it and turn what was AY.33 into AY.33.1 (or redesignated all as AY.34 and AY.34 to avoid problems).

Will submit the strains for the S:29A, S:250I parent lineage in another issue for your consideration?

Maybe hold off making a release until then.

corneliusroemer commented 3 years ago

@rmcolq I've now submitted a proposal for the parent lineage as #219 and will thus reopen this issue so that both can be considered together.

corneliusroemer commented 3 years ago

Good news, looks like the fast AY.33 expansion was driven by export from Morocco where it grew due to founder effect (where recent sequencing showed it's at ~50%, so not dominant!) image

corneliusroemer commented 3 years ago

It's a good thing this lineage has not been released. It should be released only once #219 has been resolved and removed until then. @rmcolq @chrisruis

chrisruis commented 3 years ago

Based on discussion in #219, we've updated AY.33 in v1.2.79 to start on the branch with A21647G (S:T29A), more details in #219