BA.2 + S:L452R sub-lineage in Portugal with N:221F [40 seq]

[insapathogenomics]

Emergence of a BA.2 + S:L452R sub-lineage in Portugal

By: Bioinformatics Unit, National Institute of Health Dr Ricardo Jorge (INSA), Portugal

Description
Sub-lineage of: BA.2
Earliest sequence: 2022-03-01
Most recent sequence: 2022-03-29
Countries circulating: Portugal

In Portugal, we have been monitoring a cluster of BA.2 sequences with the additional mutation Spike:L452R. The mutation "markers" of this cluster are S:L452R (nt: T22917G) and N:L221F (nt: G28936T) (see image). The first case was detected on 01 March 2022. Since then, this sub-lineage has been consecutively detected in our weekly nationwide random surveys, including cases in four regions (North, Center, Lisbon region and Alentejo) (total of 18 sequences so far).

Latest data about variant circulation in Portugal can be found at https://insaflu.insa.pt/covid19/ (weekly reports on Tuesdays).

Genomes:

<style> </style>

Sequence	GISAID ID	Collection date	Country
Portugal/PT29098/2022	EPI_ISL_10985874	01/03/2022	Portugal
Portugal/PT29787/2022	EPI_ISL_11217970	06/03/2022	Portugal
Portugal/PT30627/2022	EPI_ISL_11507322	15/03/2022	Portugal
Portugal/PT30730/2022	EPI_ISL_11507422	15/03/2022	Portugal
Portugal/PT30744/2022	EPI_ISL_11732771	20/03/2022	Portugal
Portugal/PT31042/2022	EPI_ISL_11733060	21/03/2022	Portugal
Portugal/PT30754/2022	EPI_ISL_11732781	22/03/2022	Portugal
Portugal/PT30878/2022	EPI_ISL_11732903	22/03/2022	Portugal
Portugal/PT31229/2022	EPI_ISL_11733243	22/03/2022	Portugal
Portugal/PT31355/2022	EPI_ISL_11941554	28/03/2022	Portugal
Portugal/PT31804/2022	EPI_ISL_11941986	28/03/2022	Portugal
Portugal/PT31813/2022	EPI_ISL_11941995	28/03/2022	Portugal
Portugal/PT31818/2022	EPI_ISL_11942000	28/03/2022	Portugal
Portugal/PT31824/2022	EPI_ISL_11942006	28/03/2022	Portugal
Portugal/PT31846/2022	EPI_ISL_11942026	28/03/2022	Portugal
Portugal/PT31649/2022	EPI_ISL_11941840	29/03/2022	Portugal
Portugal/PT31892/2022	EPI_ISL_11942073	29/03/2022	Portugal
Portugal/PT31895/2022	EPI_ISL_11942076	29/03/2022	Portugal

Evidence

[corneliusroemer]

Good proposal, I'd also noticed the rise of S:L452R in Portugal.

There's another mutation that always appears in this cluster: C27128T synonymous.

It's also made it to a number of countries: England, Scotland, Austria, US (MA)

Worth designating, it's well clustered, shows growth, has interesting Spike mutation, international spread.

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3AL452R%2CN%3AL221F&nucMutations=C27128T&pangoLineage=BA.2&

[insapathogenomics]

Thank you @corneliusroemer. We noticed that C27128T synonymous SNP, still, in our dataset, we have one sequence (Portugal/PT27633/2022; EPI_ISL_10122479) that has the C27128T but not the S:L452R and N:L221F (so, as C27128T is ancestral to the S:L452R and N:L221F changes, we did not included it). Curiously, this sequence was detected three weeks before the first S:L452R + N:L221F sequence and exactly in the same portuguese municipality. While preliminary, this may indicate that the S:L452R+N:L221F acquisition occurred during the community transmission in Portugal.

[InfrPopGen]

Needs time to see if this one is going to grow, and so have labelled this for monitoring.

[corneliusroemer]

I'm pretty confident it is growing - 2% in Portugal and showing up internationally.

There around 200 daily positive tests with it each day in Portugal. Considering limited testing there are probably 1k per day. It wouldn't have got so big so quickly by chance had it not got a growth advantage.

It also gets misclassified as BA.2.11 so that's another reason to label.

It's got the signature of a lineage we expect to grow, and we see growth. Yes there are only 40 sequences or so but we designated BA.4/5 when there were equally few.

https://cov-spectrum.org/explore/Portugal/AllSamples/Past6M/variants/international-comparison?aaMutations=S%3A452R%2CN%3A221&pangoLineage=BA.2*&

[FedeGueli]

@corneliusroemer agree and i woulf add it has already been sequenced in France where are concentrated the BA.2.11 sequences. I think it could really help to get this designated soon to track the potential L452mutated wave that seems growing everywhere.
Also important to keep in mind that @insapathogenomics alerted very early for AY.43 + 501S and then it resulted in one of the fastest sublineages of delta

[corneliusroemer]

The Usher tree is also very interesting. Theres's quite some diversity now

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/singleSubtreeAuspice_genome_1c7b_405080.json?c=userOrOld&label=nuc%20mutations:C6196T

[insapathogenomics]

The BA.2 + S:L452R sub-lineage (with N:L221F) keeps increasing in frequency in Portugal, representing ~4% in the latest nationwide survey (week 15; 11-17 April; survey ongoing). As already mentioned, it is "misclassified" as BA.2.11, so it would be of interest to have a different designation to better track its (inter)national dissemination.

Latest report (PT/EN) can be found at https://insaflu.insa.pt/covid19/ (weekly reports every Tuesdays).

[corneliusroemer]

Thanks @insapathogenomics, this definitely keeps on growing and is worth designating in the next round in my view @chrisruis

[InfrPopGen]

Thanks for submitting. We've added lineage BA.2.35 with 32 newly designated sequences, and 4 updated designations. Defining mutation(s) T22917G (S:L542R) and G28936T (N:L221F).

[FedeGueli]

@InfrPopGen BA.2.35 was already assigned according to the Pango.Network list:
https://www.pango.network/summary-of-designated-omicron-lineages/

"

BA.2.35	USA	C6285T (Orf1ab:T2007I)

"

[chrisruis]

Hi @FedeGueli Sorry that was my fault. That lineage was never actually added as its defining mutation wasn't specific enough. So @InfrPopGen's lineage is the real BA.2.35!

[FedeGueli]

Thank you very much @chrisruis and @InfrPopGen !