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Ryan Hisner Profile picture
@LongDesertTrain
May 26, 2021 • 7 tweets • 2 min read • Read on X
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1/7 Satan is trending on Twitter. I recall what Mark Twain said about him.
"I am quite sure that I have no race prejudices, and I think I have no color prejudices nor caste prejudices nor creed prejudices. Indeed, I know it..."
2/7 "I can stand any society. All that I care to know is that a man is a human being—that is enough for me; he can't be any worse."
3/7 "I have no special regard for Satan; but I can at least claim that I have no prejudice against him. It may even be that I lean a little his way, on account of his not having a fair show."
4/ "All religions issue bibles against him & say the most injurious things about him,but we never hear his side. We have none but the evidence for the prosecution, yet we have rendered the verdict. To my mind, this is irregular. It is un-English; it is un-American; it is French."
5/7 "We may not pay [Satan] reverence, for that would be indiscreet, but we can at least respect his talents."
6/7 "A person who has for untold centuries maintained the imposing position of spiritual head of four-fifths of the human race, and political head of the whole of it, must be granted the possession of executive abilities of the loftiest order."
7/7 "In [Satan's] large presence the other popes and politicians shrink to midges for the microscope. I would like to see him. I would rather see him and shake him by the tail than any other member of the European Concert."

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More from @LongDesertTrain

Ryan Hisner Profile picture
Jul 7
Quick 🧵on previous variants that resemble the recent Ontario SARS-2 saltation variant that's now been detected in 4 sewersheds in NYC and one in Utah.

The practical impact of these variants ranged from ~zero to modest to major. 1/10

Background 🧵👇
• BA.2.87.1 - Appeared suddenly Sept 2023, spread across South Africa, & was detected in WW in Thailand. Then basically disappeared after Dec 2023 (apart from 1 seq collected in May 2024 from Eswatini). Emerged just when JN.1 was sweeping—bad timing. 2/
• BA.2.83 - One of several BA.2 saltation variants that emerged in late 2022. First appeared in India, then in Denmark, Canada, and Australia. Could not compete with BA.2.75 and BA.5 though and disappeared without making any real impact. 3/
Read 10 tweets
Ryan Hisner Profile picture
Jul 4
A mysterious, unusually diverse saltation lineage descended from KP.3.1.1 (last seen early 2025) has circulated at a low level for ~8 months in Ontario (see 🧵on next post).

Seemed a local anomaly, but @solidevidence just spied a weird spike in NYC WW—& it's the same one!
1/14
Here's a post I made a couple weeks ago when another Ontario sequence from this lineage showed up.

2/14
The remarkable diversity of this lineage raises questions about its origin and the conditions in which it spread and evolved.

Notably, the version detected in NYC wastewater is the same as the two most recent sequences from Ontario (long, bottom branch w/2 seqs below).
3/14 Image
Read 15 tweets
Ryan Hisner Profile picture
Jun 19
Wildly diverse branch of MC.10.1.7 (KP.3.1.1 descendant, died out early 2025) in Ontario.

It's apparently been circulating at a low level for the past year. ≥6 different people are represented here.

I think this must involve one or more chronic infections + transmission. 1/7 Image
• Busy 630 loop: ∆621-622 + NVFQ->IFPMAE at S:641-644.

• 2-nuc muts: W452K + D839K.

• Ultra-rare S2 insertion: ins791P

M:H155N, ORF1a:R3164H, & ORF3a:255-256 deletions cluster in chronics, often w/S:D936H/Y or ORF1a:L3201P. Intriguingly, D936Y was in the last seq.
2/7 Image
More info on this unusual branch can be found on the Github page for undesignated lineages, which Fede Gueli tirelessly and selflessly keeps up to date.

3/7github.com/sars-cov-2-var…
Read 8 tweets
Ryan Hisner Profile picture
Jun 10
Another fantastic preprint on BA.3.2's propensity for children, this time from @yunlong_cao & co.
They not only confirm the findings of David Ho's lab (that kids have ~0 antibody response to BA.3.2) but dig into the details of exactly why kids are so vulnerable to BA.3.2.

1/4
Two big wins for vaccination & mRNA vaccines:

1. Kids vaccinated before being infected have robust antibodies against BA.3.2

2. Unvaxed adults much more vulnerable to BA.3.2, esp. compared to mRNA-vaxed adults.

Read @yunlong_cao's 🧵 & very readable paper for details. 2/4 Image
There's still one major paradox here I can't wrap my head around: countries with the highest vaccination rates & the lowest proportion of children appear—very low sequencing makes hard conclusions difficult—to have the highest proportion of BA.3.2. 3/4
Read 6 tweets
Ryan Hisner Profile picture
Jun 4
New data from David Ho's lab showing that while adults & kids have ~equal antibody responses to XFG & NB.1.8.1, children have essentially no neutralizing antibodies to BA.3.2.

This seems to largely solve the BA.3.2 + kids mystery. 1/14 Image
If you've missed the story about how BA.3.2 (a novel, divergent saltation variant) is hugely overrepresented in sequences from children, this was my original (very quick) analysis, which subsequent data extended & confirmed. 2/
More details from this preprint. 50 is the limit of detection (i.e. zero). Nearly all kids under 7 had no detectable nAbs to BA.3.2, despite robust nAb titers against NB.1.8.1 & XFG.

Notably, most kids also had zero nAbs to ancestral D614G or XBB.1.5. 3/
biorxiv.org/content/10.648…Image
Read 14 tweets
Ryan Hisner Profile picture
Mar 26
So it's clear that BA.3.2 preferentially infects children, something we have never seen before in a SARS-CoV-2 variant.

Why?

The question's baffled me, but after a suggestion from Darren Martin, I think I have an explanation that makes sense.
1/16
I've tried to make sense of BA.3.2's penchant for kids by considering its unique spike: more compact, more closed, & more antibody-evasive than any other variant.

But I think another feature of BA.3.2 is responsible: its wholesale deletion of ORF7a, ORF7b, & ORF8 (∆ORF78).
2/
∆ORF78 is rare but not unheard of; it was in several late XBB variants (GW.5.1.1, FW.1.1, GE.1.2, etc) & a few branches of other variants. I've long thought these late XBB had an advantage in some population subsector, but I didn't suspect kids.
3/
Read 18 tweets

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