ryanhisner.bsky.social
Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution.
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7,968 followers
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Not the left. The Nation never did, for example. It's really confounding to see some on the left fall for this crap. I don't understand it.
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It's been sad to see some leftist outlets & journalists swallow lab-leak fare like this. Some have even cited info-free "intelligence agency" announcements as legitimate sources, which is anathema for anyone the left (for very good reasons). I don't get it.
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Literally every virus outbreak/epidemic I’ve been involved with over the last 35 years has involved an origins conspiracy theory (HIV had multiple). My conclusion is that some people intrinsically want to assign blame to a human and cannot accept what nature does. It’s always about blame.
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Thanks for the insight into those superspreader cases. It's encouraging to know that these were easily preventable. On the other hand, the way humans have reacted to pandemic threats recently seems to ensure that a lot of easily preventable threats remain serious dangers.
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Wow, talk about an utterly insane hospital policy. I hope that situation has changed and that they've improved the ventilation and filtration in those facilities.
I recently saw a chart showing that South Korea was the only OECD country w/fewer drs per capita than the US, so that may be a cause.
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Except in those extraordinary superspreader events in South Korean hospitals. I think one person infected ~30 people and another ~80 people. So weird in a disease that, outside of those events, has never been able to sustain a long chain of transmission.
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It'd be interesting to see if there's a relationship btwn degree of innate immune evasion of the infecting variant & Long Covid. Pre-Omicron VOC, esp Alpha & Delta, potently evaded innate immunity compared to WT, while BA.1 & BA.2 had far weaker innate immune evasion compared to BA.5.
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Seems as wise as crypto or meme-coins—so should do well in today's investing environment. Judging by the ads & spam calls/emails that invade my waking hours, the US economy is mainly based on pure financial bubbles, gambling on sports, & various schemes by vampire corporations to defraud Medicare.
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💯 Mark Twain's story "Captain Stormfield's Visit to Heaven" touches on this w/regard to literary merit. A bunch of unknown, unread commoners rank far above Homer & Shakespeare in Stormfield's Heaven.
"They warn't rewarded according to their deserts, on earth, but here they get their rightful rank"
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Congratulations, Leshan! A well deserved honor.
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Oh, wow thanks. I tried to look up Tyler Starr, that account didn't show up. I don't know why the search engines at these places are so bad.
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Tyler Starr and @jbloomlab.bsky.social did great work illustrating this, though it looks like the threads on Q493E epistasis are all on Twitter. x.com/tylernstarr/...
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...the marginal, stepwise changes in spike might at some point enable a novel mutation to arise through epistasis, which is what happened last year. Q493E caused an unviably large drop in ACE2 affinity on a JN.1 spike background, but when F456L was added, Q493E actually increased ACE2 affinity.
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...if the current trend of antigenic drift marked by gradual accumulation of slight antigenic changes continues.
Of course, a completely novel variant could arise & spread at any time, which would totally change the picture. Or...
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We've gone over 1.5 years without a dramatically new, chronic infection-derived variant emerging—by far the longest gap we've had.
Last summer KP.3, w/S:Q493E, was a big antigenic change & led to a substantial summer wave. I don't see anything similar this year. I expect a long trough in cases...
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I'm so sorry to hear that. It's hard to say for sure which variant you had. If you live in the US, whether you were infected in early or late December would change the probability of which variant quite a bit.
Within the US, states will vary a lot too. New York, e.g., would have a much higher JN.1%
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I think it likely does in a lot of cases, perhaps most. It's very hard to determine the proportion of Long Covid cases that are due to persistent infection though, so there's a lot of uncertainty.
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Exactly what @jameskrieger.bsky.social said. Virtually all mutations involve 1 nuc change; 2-nuc mutations are extremely rare.
The two 2-nuc spike mutations here are even more remarkable as both involve the rarest type of nuc mutation: C->G. Q493V also requires an A->T nuc mut, another rare one.
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That's a fascinating question and one that I hope is pursued by someone (maybe @solidevidence.bsky.social?). Certain mutations in feline CoV change the infection course from a mild GI infection to the systemic FIP, which I think is usually fatal. Could something analogous be happening with EBV?
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No, the BA.1 portion of this recombinant originates around December 2021 to January 2022. There aren't any previous samples of this one.
The KP.3.1.1 portion is from mid-late 2024, though it's not possible to locate the exact branch as there are several equally plausible candidates.
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• The factor I mentioned above: chronic intrahost lineages being replaced within the host with by humdrum circulating variants
• Undersampling in regions of the world likely to have higher rates of chronic infection
• Oversampling of patients w/cancer or other condition they're being treated for
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That was @solidevidence.bsky.social's conservative, back-of-the-envelope estimate. Many factors make determining the true rate very difficult. To mention a few:
• Many chronic infections cannot be detected via traditional nasal swabs as they inhabit the deep lung, GI tract, or other bodily niche
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It's horrifying. Makes me utterly ashamed of my country, which is actively supporting these atrocities & war crimes.
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Some of the ORF1a muts are characteristic of a pattern seen in many bronchoalveolar lavage seqs, so think I could predict some of the muts from the non-ORF1a part of the BA.1.17 (that was replaced by KP.3.1.1). Not a testable hypothesis though unless an old seq from the same patient shows up. 4/4
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How often does a newer variant infect a chronically infected person & go on to completely replace the old intrahost variant, wiping out all evidence of the previous chronic infection? I suspect this happens a lot, meaning chronic infections are more common than the sequencing record suggests. 3/4
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Clearly, it comes from a ≥3-year-long BA.1 infection that was superinfected with KP.3.1.1, whose superior spike recombined with the long-evolving BA.1's ORF1a.
The retention of the BA.1 ORF1a makes it clear this person has been continuously infected for over 3 years, but I have to wonder.... 2/4
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Big jump with a very large number of mutations not seen in current variants.
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BA.3.2 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. Will it stick around long enough to acquire such mutations? It's anyone's guess.
9/end
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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
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See, e.g, @solidevidence.bsky.social'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 (undergoing a Covid wave), though how much is uncertain. 7/ lungfish-science.github.io/wastewater-d...
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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
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NB.1.8.1 and LP.8.1.1, which look like 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
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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 @jbloomlab.bsky.social has extensively explored. 4/9
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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
www.biorxiv.org/content/10.1...
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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
bsky.app/profile/ryan...
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There is no structural problem so obviously systemic that moralizing, privileged scolds won't turn it into a threadbare Sunday school homily that any clever 10-year-old can recognize for the self-serving, victim-blaming slush it is.
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Insanity. Humanity has reacted to the collective threat of disastrous climate change by... starting a new arms race. 😑
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Especially when countries everywhere are rapidly increasing funding for the tools of destruction and death, something seemingly every mainstream commentator deems "good." This is extremely depressing to me.
responsiblestatecraft.org/sipri-milita...
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Wow, that's fascinating. Is this true of phosphorylated N as well?
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Awesome! Congrats on the publication. Looking forward to reading the final version.
I was thinking of this paper just a few days ago as I read a study about a model of the replication-transcription complex proposing that dimerized N loads the TRS-L & holds it just above exiting RNA.