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**sharon sanders** · October 5, 2022, 09:34 AM

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Cornelius Roemer
@CorneliusRoemer
·
Oct 2
With 11 days more data, it is becoming quite clear that BQ.1.1 will drive a variant wave in Europe and North America before the end of November Its relative share has kept more than doubling every week It has taken just 19 days to grow 8-fold from 5 sequences to 200 sequences 1/

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Cornelius Roemer
@CorneliusRoemer
·
Sep 21

BQ.1.1 is showing quite some growth, especially in England where the first sample was submitted 9 days ago and now there are already 28 sequences. I hope there is some sort of biased sampling going on. Otherwise this doesn't look good. @PeacockFlu @kallmemeg @theosanderson
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Cornelius Roemer
@CorneliusRoemer
·
Oct 2
A week ago,
@TWenseleers
estimated a growth advantage of ~14% per day for BQ.1 over BA.5 This may be a slight overestimate. But note this was for BQ.1 not BQ.1.1 which has a few extra % pts Evidence quite strong that BQ.1.1 will have >10%/day advantage. 2/
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Tom Wenseleers
@TWenseleers
·
Sep 25
This is the calculated growth rate advantage per day plus 95% confidence intervals that I obtain from these fits. Quite sizeable, even if these early estimates may still have a bit of an upward bias.
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Cornelius Roemer
@CorneliusRoemer
·
Oct 2
For comparison: Alpha had ~7%/day growth advantage Delta had ~11%/day over Alpha BA.1 Omicron had ~20-25%/day over Delta BA.2 had ~11%/day over BA.1 BA.4/5 had ~11%/day over BA.2 Looks like BQ.1.1 is less drastic than Omicron vs Delta but comparable to Delta, BA.2 & BA.4/5 waves
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Cornelius Roemer
@CorneliusRoemer
·
Oct 2
While BQ.1.1 is significantly faster than BA.2.75.2, it could still happen that XBB, BS.1.1 or another BA.2.75* offshoot will be able to keep up with BQ.1.1, but this would not make wave dynamics better, only worse.
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Cornelius Roemer
@CorneliusRoemer
·
Oct 2
Bear in mind that variants' impact on case growth is dependent on their share of all cases: At 10% share -> only 10% of impact at 100% So with BQ.1.1 making up only maybe 2-5% of cases reported today it isn't yet a main factor behind the recent case growth we are seeing in Europe

**sharon sanders** · October 5, 2022, 09:41 AM

bio-Rxiv: Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution

**sharon sanders** · October 10, 2022, 10:10 PM

Please see:

China - State media: COVID-19 new Omicron variant BF.7 sweeps to more provinces; experts warn it will dominate domestic flare-up - October 10, 2022

China - State media: Highly contagious COVID-19 Omicron variant BA.5.1.7 identified in Chinese mainland for first time - October 10, 2022

**sharon sanders** · October 14, 2022, 12:16 AM

Cornelius Roemer
@CorneliusRoemer
·
6h
BQ.1* and XBB have different geographic foci BQ.1* is mostly in Africa, Europe and North America XBB in South (East) Asia 3 countries with similar levels worth watching for comparison and potential co-circulation are: - Japan - Australia - South Korea https://cov-spectrum.org/explore/World/AllSamples/from=2022-08-20&to=2022-10-01/variants?nextcladePangoLineage=XBB*&nextcladePango Lineage1=BQ.1.1*&analysisMode=CompareEquals&… 1/

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Cornelius Roemer
@CorneliusRoemer
·
6h
Here are the mutations that only occur in one of the two variants: XBB only: S:V83A, S:Y144-, S:H146Q, S:Q183E, S:V213E, S:G339H, S:R346T, S:L368I, S:V445P, S:G446S, S:F486S, S:F490 BQ.1.1 only: S:H69-, S:V70-, S:V213G, S:G339D, S:K444T, S:L452R, S:F486V 3/
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Cornelius Roemer
@CorneliusRoemer
·
6h
Spikes of XBB and BQ.1.1 are as different from each other as the spikes of most named variants between each other. Just because they are all called Omicron doesn't mean they are similar. XBB and BA.1 are _very_ different (16/21 mutations only in one, 20 shared, bottom right) 4/

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**sharon sanders** · October 18, 2022, 11:13 AM

New Results

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Yunlong Cao, Fanchong Jian, Jing Wang, Yuanling Yu, Weiliang Song, Ayijiang Yisimayi, Jing Wang, Ran An, Na Zhang, Yao Wang, Peng Wang, Lijuan Zhao, Haiyan Sun, Lingling Yu, Sijie Yang, Xiao Niu, Tianhe Xiao, Qingqing Gu, Fei Shao, Xiaohua Hao, Yanli Xu, Ronghua Jin, Youchun Wang, Xiaoliang Sunney Xie
doi: https://doi.org/10.1101/2022.09.15.507787
This article is a preprint and has not been certified by peer review [what does this mean?].
000013606416

Abstract

Continuous evolution of Omicron has led to numerous subvariants that exhibit growth advantage over BA.5. Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented. Despite their rapidly divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, K356, K444, L452, N460K and F486. The driving force and destination of such convergent evolution and its impact on humoral immunity established by vaccination and infection remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab. BR.2, CA.1, BQ.1.1, BM.1.1.1, and especially XBB, are the most antibody-evasive strain tested, far exceeding BA.5 and approaching SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of neutralizing antibodies and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted the convergent RBD evolution. Additionally, the precise convergent RBD mutations and evolution trends of BA.2.75/BA.5 subvariants could be inferred by integrating the neutralization-weighted DMS profiles of mAbs from various immune histories (3051 mAbs in total). Moreover, we demonstrated that as few as five additional convergent mutations based on BA.5 or BA.2.75 could completely evade most plasma samples, including those from BA.5 breakthrough infection, while retaining sufficient hACE2-binding affinity. These results suggest that current herd immunity and BA.5 vaccine boosters may not provide sufficiently broad protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be of high priority, and the constructed convergent mutants could serve to examine their effectiveness in advance.

Competing Interest Statement

X.S.X and Y.C. are co-founders of Singlomics Biopharmaceuticals and listed as inventors on patents related to DXP-604, SA55, and SA58. The remaining authors declare no competing interests.

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

https://www.biorxiv.org/content/10.1101/2022.09.15.507787v3

Continuous evolution of Omicron has led to numerous subvariants that exhibit growth advantage over BA.5. Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented. Despite their rapidly divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, K356, K444, L452, N460K and F486. The driving force and destination of such convergent evolution and its impact on humoral immunity established by vaccination and infection remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab. BR.2, CA.1, BQ.1.1, BM.1.1.1, and especially XBB, are the most antibody-evasive strain tested, far exceeding BA.5 and approaching SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of neutralizing antibodies and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted the convergent RBD evolution. Additionally, the precise convergent RBD mutations and evolution trends of BA.2.75/BA.5 subvariants could be inferred by integrating the neutralization-weighted DMS profiles of mAbs from various immune histories (3051 mAbs in total). Moreover, we demonstrated that as few as five additional convergent mutations based on BA.5 or BA.2.75 could completely evade most plasma samples, including those from BA.5 breakthrough infection, while retaining sufficient hACE2-binding affinity. These results suggest that current herd immunity and BA.5 vaccine boosters may not provide sufficiently broad protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be of high priority, and the constructed convergent mutants could serve to examine their effectiveness in advance. ### Competing Interest Statement X.S.X and Y.C. are co-founders of Singlomics Biopharmaceuticals and listed as inventors on patents related to DXP-604, SA55, and SA58. The remaining authors declare no competing interests.

**sharon sanders** · October 18, 2022, 11:27 AM

Moritz Gerstung
@MoritzGerstung
The next few months may be a tight race between the BQ.1.1 and XBB.1 SARS-CoV-2 variants. - Globally BQ.1.1 grew ~12% faster than BA.5, ranging from ~10% in Belgium to ~15% in Germany. - XBB.1 grew >20% faster than BA.5 in Singapore, ~13% in the U.S., but only ~7% in Denmark.

ALT

3:06 AM · Oct 18, 2022·Twitter for iPad
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Moritz Gerstung
@MoritzGerstung
·
9h
Replying to
@MoritzGerstung
The current uncertainty of XBB.1’s growth rate makes it an open race. - XBB.1 dominance in Asia seems given. - BQ.1.1 is widespread in Europe and North America, so it is likely that it will keep its higher share. - The rest of the world could see either outcome I think.

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Moritz Gerstung
@MoritzGerstung
·
9h
The distinct regional spread has has been noted before by
@TWenseleers
and others.
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Tom Wenseleers
@TWenseleers
·
Oct 7
In Asia, the XBB recombinant is currently the one with the largest growth advantage though, and it may also become so in Europe (I'm not showing estimate for Europe because of small sample size, but it's also growing fast there).
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Moritz Gerstung
@MoritzGerstung
·
9h
BQ.1.1 and XBB have very distinct spike mutations. - BQ.1.1 derives from BA.5. - XBB is a recombination of two BA.2 lineages (presumably during co-infection of the same individual). - Neutralisation of XBB by vaccine/infection derived antibodies was found to be weaker.
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Cornelius Roemer
@CorneliusRoemer
·
Oct 14
While BQ.1.1 and XBB share a lot of spike mutations due to their ancestry - descending from BA.2, they each have a sizeable number of unique mutations, making limited cross-protective immunity and co-circulation a possibility. Delta is included for comparison. Data: @GenSpectrum
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**sharon sanders** · October 19, 2022, 07:16 AM

This is from a "pharma" guy.

Joshua “Scotch” McClure

@joshuamcclure
·
10h
I can no longer track the number of highly concerning #COVID #variants SARS-CoV-2 is completely out of control. The virus is accelerating evolution towards combinations (a multitude) of the most dangerous, AND highly virulent. All past pharmaceutical tools border on obsolete.

**sharon sanders** · October 24, 2022, 06:37 AM

Raj Rajnarayanan
@RajlabN
#COVID19 #VariantDashboard - #UnitedStates >> Rise of BQ.1*/BQ.1.1* lineages << TOP lineages (15-DAY TRENDS): 14.8% BA.5.2.1 9.7% BA.5.2 8.5% BA.4.6 5.1% BA.5.1 5.0% BQ.1.1 3.3% BQ.1 2.5% BF.7 Tracker: http://tinyurl.com/mryj4uu7 #OmicronUpdates 10/23/22 1/n

9:49 PM · Oct 23, 2022·Twitter Web App
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Raj Rajnarayanan
@RajlabN
·
9h
Replying to
@RajlabN
Sequence count by US State Share of sequences with specimen collection dates in the last 15 days. New York has submitted a lion's share of sequences 2/n

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Raj Rajnarayanan
@RajlabN
·
9h
Top circulating lineages (#15DayTrends) 66.9% BA.5* 15.5% BQ.1* (of which 6.6 BQ.1.1*) 8.5% BA.4.6* 3.4% BA.2.75* (0.6% BM.4.1.1) 2.5% BF.7* 1.3% BA.4* 1.0% XBB* (0.8% XBB.1) 0.3% BA.2.3.20* (includes CM.2) Total # of Lineages Circulating in USA: 177 3/n

Raj Rajnarayanan
@RajlabN
·
9h
Updates from #LineageWatchTeam's
@GenSpectrum
#Collection24 maintained by
@siamosolocani
/
@Asinickle1
>> All eyes on BQ* lineages especially BQ.1.1*<< Collection24: https://cov-spectrum.org/collections/24?country=United+States&highlightedOnly=true… 7/n

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Raj Rajnarayanan
@RajlabN
·
9h
Immune Escape and ACE2 binding of top lineages in USA (relative to BA.2) Bivalent boosters (OG/Omicron.BA.5) will potentially protect the boosted from getting severe disease/hospitalizations. Please get #boosted ASAP! https://public.tableau.com/app/profile/raj.rajnarayanan/viz/ImmuneEscapevsACE2BindingrelativetoBA2-USA15DayTrends/Dashboard2… 8/n

public.tableau.com
Immune Escape vs ACE2 Binding (relative to BA2) - USA 15DayTrends
Immune Escape vs ACE2 Binding (relative to BA2) - USA 15DayTrends
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Raj Rajnarayanan
@RajlabN
·
9h
#Hospital #Capacity - (by State/Division) All hospitalizations not just COVID-19 https://public.tableau.com/app/profile/raj.rajnarayanan/viz/HospitalCapacity-USA/HospitalCapacity… 9/n

public.tableau.com
Hospital Capacity - USA
Hospital Capacity - USA
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Raj Rajnarayanan
@RajlabN
·
9h
#COVID19 #Hospitalizations in the #UnitedStates Please get #boosted (especially > 50 yr old and immune compromised) and #MaskUP! Hospital Tracker (by States, by age group): https://public.tableau.com/app/profile/raj.rajnarayanan/viz/COVID19HospitalizationsUSA/COVID19_HOSP_USA… 10/n

public.tableau.com
COVID19 Hospitalizations USA
COVID19 Hospitalizations USA
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**sharon sanders** · October 24, 2022, 09:58 AM

J Infect Public Health . The rapid emergence of multiple sublineages of Omicron (B.1.1.529) variant: Dynamic profiling via molecular phylogenetics and mutational landscape studies

**sharon sanders** · November 17, 2022, 09:38 AM

Moritz Gerstung

2h • 10 tweets • 5 min read Bookmark Save as PDF My Authors
Some musings on SARS-CoV-2 evolution

TLDR: The share of the variant zoo increased further with BQ.1* and XBB* at the top.

But there are interesting patterns underneath which can be illustrated by one exotic lineage: CH.1.1.

It’s rare, but it rises as fast as BQ.1.1. Why?
Background: There is a whole zoo of omicron sublineages, often defined by a range of mutations enabling partial immune escape.

Looking at the crude global increase over the past 28d CH.1.1 is one that has increased at the upper end of the flock.
Why does it spread as fast as BQ.1.1?

It turns out that it has independently acquired *the same set of key RBD mutations* as BQ.1.1.

Yet CH.1.1 derives from BA.2, while BQ.1.1 is a descendant of BA.5 though.
CH.1.1 makes up about 1% of cases in the U.K., 2% in Australia and 1-3% across Asia.

BQ.1.1 comprises 10-60% of cases except for Asia and Oceania.

The freq of CH.1.1 is considerably lower because it started spreading around *a month later later* than BQ.1.1, around October
So timing and location matter in a race with many lineages of almost equal potential.

This makes it very difficult to predict the eventual winner.

It may be that CH.1.1 ends up as a footnote.

Whoever wins though is very likely to have predictable characteristics.
The fact that the number of RBD variants leads to consistent selective advantages has been demonstrated before, eg in analyses by @TWenseleers and @CorneliusRoemer

But the extent and consistency of convergence has intriguing consequences.

Unroll available on Thread Reader

This mode of evolution is in stark contrast to the saltations of Alpha, Delta and Omicron which emerged with ~10-30 concomitant mutations.

One interpretation of these jumps is that they adapted the large spike protein to better fit to human cells.

Such events are unpredictable.
The gradual immune escape we saw recently, however, is not.

Many of the RBD mutations have been predicted earlier this year as immune escape routes in experiments by @jbloom_lab and @yunlong_cao.

There’s even an online calculator.

OverviewInteractive visualizations of deep mutational scanning measurements of RBD mutations that escape antibody binding.https://jbloomlab.github.io/SARS2_RB...s/escape-calc/
So the emergence of the recent variant zoo followed predictable patterns.

This I think is reason to be optimistic that we can get ahead of SARS-CoV-2 (and other viruses’) evolution — and design better vaccines.

(At least sometimes, as black swans may also still arise.)
Latest analysis report on github. Data aggregated by cov-spectrum from GISAID.

GitHub - gerstung-lab/SARS-CoV-2-International: International SARS-CoV-2 surveillanceInternational SARS-CoV-2 surveillance. Contribute to gerstung-lab/SARS-CoV-2-International development by creating an account on GitHub.https://github.com/gerstung-lab/SARS...-International
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**sharon sanders** · November 18, 2022, 08:24 AM

bump this

**sharon sanders** · December 30, 2022, 02:27 PM

Please see:

CDC Nowcast: A New Dominant Variant (XBB.1.5) For A New Year

Announcement

COVID-19 variants going into fall and winter 2022/2023: BA.2.75, BA.4, BQ.1.1, BA.2, XBB, BS.1.1, BF.7, BA.5.1.7.....

COVID-19 variants going into fall and winter 2022/2023: BA.2.75, BA.4, BQ.1.1, BA.2, XBB, BS.1.1, BF.7, BA.5.1.7.....

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