Sub-lineage of CH.1.1.4 with S:D839N. 55 sequences (Austria, Germany, Denmark, Croatia)

BorisUitham commented 1 year ago

Description: Sub-lineage of CH.1.1.4 with S:D839N Earliest sequence: 2022-11-14 Most recent sequence: 2023-01-12 Countries circulating: Austria (38 sequences): 34 Vorarlberg, 3 Tyrol, 1 Lower Austria. Denmark (1 sequence): 1 Midtjylland. Germany (2 sequences): 2 Baden-Württemberg GISAID query: Spike_P681R, Spike_D839N, Spike_F486S

Genomes EPI_ISL_15915165, EPI_ISL_15995866, EPI_ISL_16064877, EPI_ISL_16064888, EPI_ISL_16064938, EPI_ISL_16164357, EPI_ISL_16164369, EPI_ISL_16164466, EPI_ISL_16164533, EPI_ISL_16164581, EPI_ISL_16164711, EPI_ISL_16243487, EPI_ISL_16262625, EPI_ISL_16263657, EPI_ISL_16263679, EPI_ISL_16263693, EPI_ISL_16263749, EPI_ISL_16263756, EPI_ISL_16420466, EPI_ISL_16421634, EPI_ISL_16421638, EPI_ISL_16421662, EPI_ISL_16421665, EPI_ISL_16421667, EPI_ISL_16421678, EPI_ISL_16421688-16421689, EPI_ISL_16421698, EPI_ISL_16421714, EPI_ISL_16421728, EPI_ISL_16421745, EPI_ISL_16421752

Usher Tree Only one sample is fully sequenced and able to be placed in a phylogenetic tree. This shows the relation to CH.1.1.4. ch 1 1 4 1

Covspectrum query: https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=s%3Ad839n%2Cs%3Ap681r&nextcladePangoLineage=ch.1.1*&

Growth advantage: The recently designated CH.1.1.4 (when excluding samples with d839n) seems to be at a growth disadvantage and has not spread much. However, when comparing CH.1.1.4 + D839N with a baseline of CH.1.1, there is an advantage of 53% (22-83) over ch.1.1 in austria. In vorarlberg alone, this is 68% (31-104) and predicts 68% of CH.1.1 samples on 09-01 to be CH.1.1.4 + D839N. For comparison, CH.1.1.4 minus D839N has a calculated advantage over ch.1.1 of -12 (-23 - 0) in austria and -7 (-20 - 5) in vorarlberg. Thus the growth advantage over CH.1.1. When looking at growth advantage over current variant mix, this is 78% (46 - 111) in austria and 85% (51 - 119) in vorarlberg. This would predict a prevalence of 26.07% (10.98 - 41.17) in vorarlberg on 09-01-2023, although i'm not certain on how accurate this is. Since “pure” CH.1.1.4 is not growing much anymore and yet this added mutation is, I would like to propose this as a further sublineage.

Sidenotes: D839N is a rare mutation, only being found in 909 samples since start of pandemic. Interestingly, most of these were during delta where a p681r was present as there is now: 69.70% of d839n in the 909 samples were with p681r. However even during delta this combo was only max 0.02% of all samples. Could it be that 681r allows for a stable 839n?

According to the following source from 2021, 839N might reduce fusogenicity. Extrapolation to omicron background is unknown. Barrett CT, Neal HE, Edmonds K, Moncman CL, Thompson R, Branttie JM, Boggs KB, Wu C-Y, Leung DW, Dutch RE (2021) Effect of clinical isolate or cleavage site mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion. J Biol Chem 297:100902

BorisUitham commented 1 year ago

Since last week, + 1 sequence from Vorarlberg, Austria and +1 from Midtjylland, Denmark. Curiously, the sequence from Denmark also has I844V, another very rare mutation (2236 sequences as of today) and in close proximity to 839N

ryhisner commented 1 year ago

I'm pretty sure these two CH.1.1 uploaded from Germany belong to this lineage, but a lot of labs in Germany seem unable to sequence S:681, so no mutation is registered there on either. EPI_ISL_16597614, EPI_ISL_16597640

BorisUitham commented 1 year ago

Thank you, nextclade also assigns them CH.1.1.4 so it does seem that way. Edit: A hack-y way to catch all current 41 cases without searching for 681r could be: Spike_D839N, Spike_F486S, T23773C