HV.1 sublineage with ORF1a:T4083M first detected in California, USA (52 GISAID seqs as of 2023-08-30; USA, Canada, China, Ecuador)

[alurqu]

There may be a HV.1 sublineage with ORF1a:T4083M (C12513T; NSP8:T141M) first detected in Arizona, USA.

As of 2023-08-25, Cov-Spectrum reports 21 good-quality (22 total) HV.1+ORF1a:4083M sequences. Source: https://cov-spectrum.org/explore/World/AllSamples/AllTimes/variants?variantQuery=nextcladePangoLineage%3AHV.1+%26+ORF1a%3AT4083M&nextcladeQcOverallScoreTo=29&

There are not yet enough sequences to reliably estimate a growth advantage, but this lineage is a sublineage of a fast parent lineage, has spread to 3 countries on 2 continents including 2 non-adjacent Canadian provinces and 17 American states, has additional sequences appearing in GISAID, and it has an additional mutation ORF1a:T4083M (aka NSP8:T141M) that Bloom and Neher's estimates show as providing a growth advantage in all clades.

As of 2023-08-25, UShER shows all of the CoV-Spectrum samples are on a single subtree with evidence of additional branching: To visualize on UShER: https://nextstrain.org/fetch/github.com/alurqu/pango-designation-support-alurqu/raw/main/2023/08/subtreeAuspice1_genome_CoV-Spectrum_HV.1%2BORF1a_4083M.json?c=gt-ORF1ab_4083&label=id%3Anode_6908889

GISAID query: Spike_F486P, Spike_F456L, Spike_Q52H, Spike_F157L, NSP3_S1039L, Spike_L452R, NSP8_T141M Nucleotides only Query: C12513T,C22033A, C5835T (Edited)

First GISAID sequence: California, USA 2023-07-24

Most Recent GISAID sequence: North Carolina, USA 2023-08-15

A zip archive of GenBank-formatted and derived metadata and FASTA files plus CoV-Spectrum-derived UShER output files for these sequences is available at Support-HV.1+ORF1a_4083M.zip

A CoV-Spectrum list of GISAID EPI ISLs for good-quality sequences is available at gisaid-epi-isl-HV.1+ORF1a_4083M.txt

Potential effects of the non-synonymous mutation on viral relative fitness

Now to consider the clade-specific Bloom and Neher estimates (from https://github.com/jbloomlab/SARS2-mut-fitness/blob/main/results/aa_fitness/aamut_fitness_by_clade.csv) of the fitness effects of the non-synonymous mutations in their order on the UShER tree:

For ORF1a:T4083M,

clade,gene,aa_mutation,delta_fitness 20A,ORF1ab,T4083M,1.3672 20B,ORF1ab,T4083M,1.2216 20C,ORF1ab,T4083M,1.308 20E,ORF1ab,T4083M,1.2706 20G,ORF1ab,T4083M,1.5972 20I,ORF1ab,T4083M,0.97347 21C,ORF1ab,T4083M,1.6464 21I,ORF1ab,T4083M,1.2674 21J,ORF1ab,T4083M,1.3126 21K,ORF1ab,T4083M,1.1227 21L,ORF1ab,T4083M,0.62093 22A,ORF1ab,T4083M,0.57972 22B,ORF1ab,T4083M,0.98779 22C,ORF1ab,T4083M,0.64668 22D,ORF1ab,T4083M,0.27632 22E,ORF1ab,T4083M,0.82636 22F,ORF1ab,T4083M,1.0486 23A,ORF1ab,T4083M,0.63056

[FedeGueli]

Orf1a:T4083M was also in some AY.4 sublineages very homoplasic on that backbone.

[FedeGueli]

I looked back at 2021 it seems it gave a substantial advantage over Delta baseline (in the pic is Denmark)

[FedeGueli]

Already up to 43 multiple american states and Ontario

[FedeGueli]

49 now. @alurqu i urge you to propose it.

[jasondorjeshort]

The recent growth of HV.1 is as out-of-the-blue as it is rapid. While it's not certain that this is real, attention needs to be given not just to its descendants but to any other S:452R sequences popping up.

XBB+S:452R has never been competitive before, and now it's outgrowing everything else by 30-50% a week on quite limited sampling. This lineage is also unusual in that it seemingly originates in a country with good sequencing, giving a very good view of its growth. At 99 US sequences the lineage is not quite in range of reliable models, yet it models as becoming the most numerous US lineage within about 3 weeks with roughly weekly absolute doubling. It could be driven by substantial immune escape, unlike other currently fast-growing lineages. But all that makes no sense given that other XBB+452R lineages have appeared and simply not grown.

Most of this growth is in a period of low absolute prevalence, indicating little change to population immunity. There hasn't been a large cross-variant inflection point in US growth since March (a small upward inflection due to either seasonality or waning immunity from BQ.1 infections is possible, but should affect XBB* equally). It's possible that the growth rate of HV.1 will turn out to be an illusion, but we shouldn't count on this happening just because it always did during the high absolute prevalence of fall 2022.

Pan-variant growth implies a downward inflection point will happen very soon. This might advantage 452R if it provides significant escape from the other XBBs, unlike the fall-2022 scenario where inflection points sent population immunity in the same direction as growing variants were already utilizing. Antibody titers of both previous infection combos and XBB.1.5 vaccination might turn out to be useful in predicting a level of population susceptibility - if the growth does turn out to be real.

[FedeGueli]

The recent growth of HV.1 is as out-of-the-blue as it is rapid. While it's not certain that this is real, attention needs to be given not just to its descendants but to any other S:452R sequences popping up.

XBB+S:452R has never been competitive before, and now it's outgrowing everything else by 30-50% a week on quite limited sampling. This lineage is also unusual in that it seemingly originates in a country with good sequencing, giving a very good view of its growth. At 99 US sequences the lineage is not quite in range of reliable models, yet it models as becoming the most numerous US lineage within about 3 weeks with roughly weekly absolute doubling. It could be driven by substantial immune escape, unlike other currently fast-growing lineages. But all that makes no sense given that other XBB+452R lineages have appeared and simply not grown.

Most of this growth is in a period of low absolute prevalence, indicating little change to population immunity. There hasn't been a large cross-variant inflection point in US growth since March (a small upward inflection due to either seasonality or waning immunity from BQ.1 infections is possible, but should affect XBB* equally). It's possible that the growth rate of HV.1 will turn out to be an illusion, but we shouldn't count on this happening just because it always did during the high absolute prevalence of fall 2022.

Pan-variant growth implies a downward inflection point will happen very soon. This might advantage 452R if it provides significant escape from the other XBBs, unlike the fall-2022 scenario where inflection points sent population immunity in the same direction as growing variants were already utilizing. Antibody titers of both previous infection combos and XBB.1.5 vaccination might turn out to be useful in predicting a level of population susceptibility - if the growth does turn out to be real.

Thank you for your analysis.