Share this page!

Enter URL or ID to Unroll

You can paste full URL like: https://x.com/threadreaderapp/status/1644127596119195649
or just the ID like: 1644127596119195649

How to get URL link on X (Twitter) App

  1. On the Twitter thread, click on or icon on the bottom
  2. Click again on or Share Via icon
  3. Click on Copy Link to Tweet
  4. Paste it above and click "Unroll Thread"!
  5. More info at Twitter Help
Ryan Hisner Profile picture
@LongDesertTrain
May 2 • 9 tweets • 4 min read • Read on X
Scrolly
Incredible how quickly @yunlong_cao & co provide us w/info on the latest emerging SARS-CoV-2 variants.

Already, we have great data on BA.3.2 (the divergent saltation lineage detected in South Africa & the Netherlands & NB.1.8.1, an emerging contender for global dominance. 1/9 Image
Image
BA.3.2 is a clear outlier on the antigenic cartography map—as expected given the enormous differences between its spike protein & every other circulating variant. 2/9
Image
It's unsurprising, therefore, that BA.3.2 evades antibodies from human sera more effectively than any other variant, though the degree of its superiority is striking. 3/9
biorxiv.org/content/10.110…Image
Then why hasn't BA.3.2 grown and spread very much? Its ACE2 binding is quite weak, & most of this is due to its tendency to be in the "closed" RBD conformation, which helps evade antibodies but reduces ACE2 interaction & infectivity, a topic @jbloom_lab has explored. 4/9 Image
NB.1.8.1 and LP.8.1.1, which seem the two most likely contenders for future dominance, have quite similar spikes, though NB.1.8.1 exhibits slightly greater antibody evasion here. However, the sera was from patients in China, where NB.1.8.1 has had its greatest success. 5/9 Image
The population immunity environment is still, IMO, different in China (& to some extent in Japan, AUS, & NZ) than elsewhere, so whether this translates into rapid global growth is still an open question. However, NB.1.8.1 is starting to appear & grow a bit in USA & Canada. 6/9
See, for example, @SolidEvidence's excellent wastewater surveillance tool, Lungfish. While only at 1-2%, NB.1.8.1 mutations are growing. Some of this may be due to exports from China (which may be undergoing a Covid wave), though how much is uncertain. 7/ lungfish-science.github.io/wastewater-das…Image
Regardless of whether LP.8.1.1 or NB.1.8.1 wins out, the spike changes in both are modest compared to the variants of the past 8-10 months, so I don't think either is likely to have a significant effect on overall case levels.
8/9
BA.3.2, on the other hand, has characteristics of a variant that could drive a global wave, but its closed spike & weak ACE2 interaction mean that it would need to acquire additional adaptations in order to be widely successful. 9/end Image

• • •

Missing some Tweet in this thread? You can try to force a refresh
　

Keep Current with Ryan Hisner

Ryan Hisner Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @LongDesertTrain

Ryan Hisner Profile picture
May 15
@DameSunshine @SharonBurnabyBC B.1.1.529 wasn't/isn't a real variant; it's a placeholder that represents a putative ancestor of BA.1/BA.2/BA.3.

Bad sequences and/or coinfections tend to get categorized as B.1.1.529:—they have enough Omicron muts to be ID'd as Omicron but so much dropout/mixed signals...
1/
@DameSunshine @SharonBurnabyBC ...that a specific designation isn't possible. Travel sequencing in the US is done by Ginkgo Bioworks. Their sequences are generally poor quality & they upload *pooled* sequences—against database guidelines. The B.1.1.529 here are likely low-quality/pooled sequences from GBW.
2/
@DameSunshine @SharonBurnabyBC I think it's entirely possible that a new, divergent variant will emerge this summer. There are hints with BA.3.2 & a 50-spike-mutation BQ.1.1 that has transmitted at least once. Other similar chronic infection-derived variants are undoubtedly lurking all over, unsequenced.... 3/
Read 4 tweets
Ryan Hisner Profile picture
Apr 25
About 1 month after this monster BQ.1.1 appeared, an even more extreme sequence has shown up in Alberta. Like the BQ, it has 50 private spike mutations, but it also has >40 AA mutations elsewhere in the genome. 1/6 Image
They include the full panoply of NSP3, NSP12, & N muts I've written about previously. ORF1a:S4398L is the most common mutation in the 4395-4398 region, this has ∆S4398, a rarity also seen in a few other extremely divergent seqs w/this constellation. 2/6 Image
In a theme that's become familiar, it's added two spike NTD glycans, N30 (via F32S) and N155 (via S155N+F157S).
Another chronic-infection leitmotif (first noted by @SolidEvidence): reversions to common or consensus residues in related Bat-CoVs, including SARS-1. 3/6 Image
Read 6 tweets
Ryan Hisner Profile picture
Apr 10
A fascinating SARS-CoV-2 sequence was recently uploaded—collected from a dog in Kazakhstan in July 2022.

Usher places the seq 1 nuc mut from the Wuhan ref seq—C21846T/S:T95I—i.e. pre-D614G. Could this seq somehow have a close connection to the first days of the pandemic?
1/19 Image
Of the sequences near this one on the tree, all are low-quality & clearly bad BA.1 or Delta sequences. The only genuine one is from the UK, collected April 2020. So it's likely even S:T95I was not inherited.

This sequence has several fascinating aspects. 2/ Image
(This all assumes the sequence is accurate and that C241T & C14408T (ORF1b:P314L) are genuinely absent. Its mutational characteristics make me certain this is a good sequence, though it's not impossible there's dropout not indicated hiding C241T and/or C14408T.) 3/
Read 19 tweets
Ryan Hisner Profile picture
Mar 12
Do you remember BA.3—the weakling cousin of BA.1 & BA.2 that seemed to take the worst from each & had weaker ACE2 binding than even the ancestral Wuhan Virus?

After 3 years, BA.3 is back.

And it is transmitting.

Who saw this coming?
1/13 Image
While the full extent of the new BA.3’s spread is not known, it’s been detected in 2 different South African regions through regular (not targeted) surveillance by @Dikeled61970012, @Tuliodna, & the invaluable South African virology community.
2/13
github.com/cov-lineages/p…
After nearly 3 years of intrahost evolution in a chronically infected person, the new BA.3 is almost unrecognizable. It has ~41 spike AA substitutions (4 of which are 2-nuc muts) to go with 14 AA deletions (∆136-147+∆243-244). We’ve seen nothing like this since 2023.
3/13 Image
Read 13 tweets
Ryan Hisner Profile picture
Jan 2
Two quick notes on the state of chronic-infection SARS-CoV-2 seqs

#1) ~3 years after its peak, BA.1 is still showing up in nasal swab seqs—despite reduced surveillance—most recently a mid-late Dec BA.1 from Nebraska.

#2) Chronic JN.1 seqs now more common, w/1 peculiarity

1/12
While BA.1 still show up semi-regularly, pre-Omicron seqs are much rarer. Why? I think there are four major reasons, two obvious & two less obvious.

A) Time.
This one’s obvious: Over time, some chronic infections are cleared, while in other cases, the host dies.

2/12
B) Number of infections.

BA.1 infected more people, more quickly than any previous variant. More infections = more chances to establish long-term infection.
3/12 Image
Read 12 tweets
Ryan Hisner Profile picture
Dec 23, 2024
Fantastic review on chronic SARS-CoV-2 infections by virological superstars Richard Neher & Alex Sigal in Nature Microbiology. I’ll do a short overview, outline a couple minor quibbles, & defend the honor of ORF9b w/some stats & 3 striking sequences from the past week.
1/64 Image
First, let me say that this is well-written, extremely readable, and accessible to non-experts, so you should go read the full paper yourself, if you can find a way to access it. (Just realized it’s paywalled, ugh.) 2/64nature.com/articles/s4157…
Neher & Sigal focus on the 2 most important aspects of SARS-CoV-2 persistence: its relationship to Long Covid (including increased risk of adverse health events) & its vital importance to the evolution of SARS-CoV-2 variants. I’ll focus on the evolutionary aspects.
3/64 Image
Read 64 tweets

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us!

Send Email!

:(