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Ryan Hisner
@LongDesertTrain
Teacher "Be ruthless with systems and be kind to people." Michael Brooks, 1983-2020
Joined May 2018
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    While the final outcome for BA.3.2 is uncertain, its unique characteristics—extensively remodeled spike NTD & SD1/SD2, novel S2 muts, & total deletion of ORF7a/7b/8—make it the best candidate for co-dominance we've seen, which could mark a new era in SARS-2 evolution. 1/
    BA.3.2 was first detected in South Africa 🇿🇦 in November 2024. Never reached dominance, never disappeard. 14 months after its emergence it accounts for 20% of all sequences. Unusual. #BA32
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    1/6 Important new study from Japan finds that with Omicron, infectious viral loads peak 3-6 days after symptom onset/diagnosis. So many people are ending isolation & returning to work & school at peak infectiousness. Thanks, @CDCgov. h/t @gianlucac1 niid.go.jp/niid/en/2019-n…
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    So I recently discovered maybe the scariest SARS-CoV-2 sequence since Omicron. Like Omicron, it possesses many infamous mutations known to confer immune escape & transmissibility. Unlike Omicron, it does not appear to have any severity-attenuating mutations, e.g. N969K. 1/12
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    It seems more certain than ever: getting Covid is bad for your brain. This study, which found cognitive effects at 1 year post Covid to be equivalent to brain aging from age 50 to 70, looked only at hospitalized patients. But as Dr. Topol says.... 1/7
    The brain injury 1 year post-Covid hospitalization, systematically assessed with MRI (reduced grey matter), biomarkers, and cognitive deficits "equivalent in magnitude to aging from 50 to 70 years of age." nature.com/articles/s4159… @NatureMedicine @gkwood3 @BenedictNeuro
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    Dude gets 217 Covid shots. Result? No adverse effects. Modestly improved immunity to SARS-CoV-2 & zero infections. Immunity to other pathogens unimpaired. Single case, but if Covid shots were as toxic as some would have it, it's hard to believe this person would be doing so well
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    Approval for molnupiravir (MOV) use should be revoked worldwide. Not only has it proven ineffective, it seems clearly to be creating sequences such as the one below, which in ~2 months acquired 72 mutations, more than its lineage had accumulated in ~3 years of evolution. 1/
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    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
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    Getting a bivalent booster is a no-brainer. It increases neutralizing antibody titers against the two dominant variants (BQ.1.1 & XBB) approximately 10-fold. It would be foolish not to get boosted. 1/
    Our latest publication on the neutralizing ability of bivalent mRNA vaccines against BQ.1.1, BF.7, and XBB.1 is out now in @NEJM TL;DR : Bivalent boosters are good boosters and induce nAbs against BQ.1.1 and XBB.1 @BarouchLab @airisyc @ocpowers5599 nejm.org/doi/full/10.10…
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    One of the great unsolved mysteries of the pandemic: SARS-CoV-2's ongoing shift toward exclusively utilizing cleaved ACE2—common in the GI tract & rare in the lungs—a trend we now know has dramatically accelerated with JN.1. This is not just an immune-evasion variant. 1/2
    Evolutionary trajectory of SARS CoV-2 from Ancestral Clade A to JN.1. What does the below mean? The virus is consolidating towards a specific pool of ACE2. Early on the ACE2 pool the virus favoured needed to be cut/cleaved. Now it heavily favours (well for JN.1) uncleave ACE2.
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    No one seems to know what BA.2 means for the world. I'm not aware of any studies on it, but I hope they come out soon. It seems apparent BA.2 will become dominant everywhere before long—as it already has in Denmark. 🧵 of graphs comparing BA.1 & BA.2 in various countries 1/16
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    This is crazy. SARS-CoV-2 wastewater levels in Austria. Have we ever seen anything like this? Levels in Ludesch are quadruple what they were at the peak of the BA.1/BA.2 wave. Ludesch is an outlier, but most other regions have also surpassed their previous all-time peaks. Wild.
    Replying to @ejustin46 @LongDesertTrain and @GourlaySyd
    Remains to be seen if the trend continues, but we are observing local freak outliers right now which in my mind could have to do with JN.1 taking over. JN.1 probably about to reach dominance nationwide. But data too sparse to tell for sure. We know soon if stage 2 ignites.
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    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
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    BA.2.86 (Pirola) is in Switzerland wastewater. If we had good wastewater surveillance throughout the world, we would have a much better idea of how widespread this is. Unbelievable that funding for wastewater surveillance is being slashed in many countries.
    BA.2.86 has been detected in wastewater samples from Switzerland (Laupen; canton Bern) taken on Aug. 5 and 6. Its frequency is rather uncertain, somewhere around 2%. The other 13 monitored locations across the country do not show a signal for BA.2.86-defining mutations yet. 1/2
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    I've probably analyzed more chronic-infection sequences than anyone, and this is the most extreme sequence I've ever seen. It has ~115 private mutations & ~37 spike mutations. A short 🧵 discussing some of what makes it remarkable, along with some speculations. 1/18
    New winner. Credit to @LongDesertTrain Delta derivative. About 100 private mutations. Collected last month (not from the US). dN/dS in Spike is off the charts. Chalked full of classic cryptic mutations.