Ryan Hisner
@LongDesertTrain
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Teacher "Be ruthless with systems and be kind to people." Michael Brooks, 1983-2020
Joined May 2018
TL;DR—Among mutations common in chronic infections are two in PLpro, which combats innate immunity. Both mutations change the SARS-2 to a SARS-1-type AA & have clear effects—remarkable intrahost functional convergence. Then questions + wild speculation at thread's end. 1/58.
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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.
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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.".@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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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.
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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.
@ejustin46 @LongDesertTrain @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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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.
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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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@EricTopol @jclinicalinvest @MedUni_Wien IMO, the realization that Epstein-Barr is the major cause of multiple sclerosis should've instantly galvanized an Operation Warp Speed-like effort to produce an EBV vaccine. Each passing month without one represents how many thousand potentially preventable cases of MS?.
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1/6 At a private gathering of 33 Pfizer-triple-vaccinated health care workers in the Faroe Islands, 21 were infected with Omicron—a superspreading event among 3-dose-vaccinated people. All received dose #3 within 2.5 months of the event. Very discouraging.
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This is a pretty amazing story. Some small subset of people have SARS-CoV-2 multiplying at insane rates in their GI tract, apparently for years. We seem to know next to nothing about the details of how Covid infects the GI tract & what effects it has there. 1/2.
For those of you that have asked me why I am convinced that cryptic lineages are coming from people, I can finally point to a pre-print with @dho and many fantastic collaborators in the UWisc and Wisc Public Health.
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It's hard to put it any better than @jljcolorado: "Droplets & surfaces are very convenient for people in power—all the responsibility is on the individual. if you admit it is airborne, institutions, governments, & companies have to do something." 3/3.(Credit to @mdc_martinus)
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Charles Chaplin, ultra-influential author and public health official in the early 1900s, said almost the exact same thing. If disease is airborne, people will despair & not be properly sanitary. Therefore, we must tell them disease is not airborne. 1/3 .
Oh boy. This video is stunning. I'm a priest, so I'm an expert in wishful thinking. This guy. he's living in fantasy land. 😮"the reason I want to believe that". Who said science is rational. 🙄
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Minimize the number of times you get Covid. Your body will thank you. Not only can repeat infections inflict Long Covid, they also, as @zalaly has shown, increase the risk of a multitude of ailments, such as cardiovascular events. 1/5.
Data from @StatCan_eng showing reinfection contributes additional risk of #LongCovid. How many cases of #LongCovid could have been prevented if we took reinfection seriously?.
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KP.3, w/the unusual Q493E mutation, now dominant globally. To me, it's the first major spike change—involving real structural/epistatic change as opposed to treadmilling, stepwise antibody-evasion mutations merely keeping pace w/population immunity—since JN.1 emerged. 1/23.
Likely this week we have already a new dominant lineage worlwide it is KP.3* . It joins the club of dominant lineages B.1 B.1.1 Alpha Delta BA.1 BA.2 Ba.5 BA.5.2 BA.5.3, BA.5.3.1,BE.1*, XBB.1.5 , XBB.1.9* XBB.1.9.2*, EG.5.1, BA.2.86, BA.2.86.1 JN.1* JN.1.11* JN.1.11.1*.
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H5N1 influenza now very likely transmitting between cows in multiple US states. The list of mammal species affected by H5N1 keeps growing and growing. 1/2.
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A single person is crapping out more SARS-CoV-2 viral genomes than has ever been recorded for this entire sewershed. Another excellent thread on cryptic lineages by @SolidEvidence. What are the short-term & long-term effects of prolonged infection? An important question. 1/3.
Second, the signal is increasing with time. Washington Court House had its highest SARS-CoV-2 wastewater levels ever in May, and the most recent sequencing indicates that this is entirely the cryptic lineage. 3/
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Cuba, thanks to elite researchers like @FabrizioChiodo, has likely created the best Covid vaccine in the world—all with public funding, no patent monopoly required. The policy implications are massive & obvious, hence the media blackout on this incredible achievement. 1/3.
"Real-World Effectiveness of the Soberana02 and Soberana-Plus Vaccine Combination in Children 2 to 11 Years of Age during the SARS-CoV-2 Omicron Wave in Cuba: A Regression Discontinuity Study". @FinlayInstituto. @SSRN .
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What should be a higher priority for society, preventing pigs from becoming sick or preventing human illness? Personally, I place a higher value on preventing human illness. I think most would agree. Why, then, are pig barns much better ventilated than schools? 1/40
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Yikes. CH.1.1 is one of the most immune-evasive variants out there & now a few have picked up Delta's P681R mutation. CH.1.1 is a BA.2.75 descendant with R346T, K444T, L452R, and F486S—similar to BQ.1.1 but with a much more immune-evasive NTD (spike residues 14-305). 1/2.
The rapidly growing lineage CH.1.1. is found mostly in Vorarlberg. Unfortunately and as a worldwide first we see position P681 mutated from H as in Omicron to R as in Delta for 3 weeks and in 12 cases now. This position is relevant for cell-cell fusion!.4/5
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What is the most fascinating and vitally important mystery of the Covid pandemic? It's not the origins of SARS-CoV-2—it's the Cryptics. This is one of the most fascinating and well-written articles on Covid I've read. 1/ .
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@People4Bernie @BernieSanders @McDonalds They didn't choose to do the right thing in those other countries—they were forced to. "Power concedes nothing without a demand."
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1/ Monica Gandhi is living proof that, if you tell people what they want to hear, you will never lack for an audience, nor will you ever run out of major media outlets eager to disseminate your tripe—even if you've been embarrassingly wrong again and again and again.
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1/ Can't put it better than @micah_arsham does here. The CDC treats the public like 1st-graders. Their job is to inform & advise the public, warning of any imminent dangers, & they've utterly failed. People will be blind-sided, with grim consequences.
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Two more sequences of this 2nd-generation BA.2 lineage just showed up in Denmark. This is the real deal. There are slight differences between the three sequences, but they are nearly identical. Below is my preliminary summary of the mutations it has on top of BA.2. 1/2
How wild can it gets?.One of our labs in Israel just uploaded a sample to @GISAID (EPI_ISL_18096761) from a patient which is not chronic nor infected by one (mans able to transmit inter host). It's so wild I had to consult with some colleagues(*) to analyze if it's not BA.6.
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Recently, I described a SARS-CoV-2 sequence that acquired 72 mutations in ~2 months, more than had evolved in the previous 3 years. Shortly after, a 123-mutation sequence was found by @OliasDave. Both bear the stamp of molnupiravir treatment. And 123 mutations is an undercount 1/
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It's easy to forget, but in spring 2021, many were arguing we didn't need to worry about Delta because the first sequences had appeared months before. If Delta was a real threat, they argued, it should have swept the field in the intervening months.
These were the US Delta samples collected in March 2021. Not every outbreak starts hot, sometimes it has to reach critical mass. It is too soon to say what BA.2.86 is going to do.
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3/ John Barry, author of The Great Influenza, on the *fundamental lesson* of the 1918 pandemic: ."Those in authority must retain the public’s trust. The way to do that is to distort nothing, to put the best face on nothing, to try to manipulate no one" .
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1/11 Shocking and terrible news, possibly for the entire world. Molnupiravir works by inducing mutations in the virus. The potential danger is obvious, and Merck has not provided any reassuring data on this.
😭Dismayed that FDA has now made the worst decision in its history. We cannot give up on raising awareness of the dangers of molnupiravir, and its poor efficacy. We must limit its use while we work on a worldwide campaign to reverse this.
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I think this preprint, by @Stuartturville, is potentially one of the more important recent SARS-CoV-2 papers. It promises to unwrap some of the most mystifying aspects of Omicron surrounding cell entry, TMPRSS2 use, & reduced lung invasion/pneumonia. 1/48.
Images of SARS-CoV-2 cultures often tell us a thousand words. Here we have the Omicron lineage XBB.1.5 growing in two engineered cells. Both equally express ACE2 and TMPRSS2. Visually this sums up our journey into the complicated entry pathway of Omicron lineages. 1/
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Something’s happening here: BA.2.86 and the furin cleavage site (FCS). The FCS has been highly conserved in all SARS-CoV-2 lineages. Why is it disappearing so much more frequently in BA.2.86/JN.1? 1/16
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5/6 Will the CDC "follow the science" & revise their 5-day, no-exit-test isolation period in light of these results? Or was that guideline based entirely on political & economic considerations (i.e. the desires of the wealthy & well-connected political donors)? Take a guess.
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Today I discovered an extraordinary microlineage of BA.2.3. What makes it extraordinary? A colossal genetic saltation (10 spike mutations) combined with striking geographic spread for a very small number of sequences (just 4 so far). 1/25
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Honored to be featured alongside @JosetteSchoenma, @Asinickle1, @nzm8qs, & @siamosolocani in this article from @guardian that contains quotes from @PeacockFlu, @shay_fleishon, and @TRyanGregory. Many thanks to author @LindaGeddes for the excellent story!
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@EricTopol @KPSCalResearch Thanks for this, Dr. Topol!. Has the importance of frequently updating vaccines ever been more clear? Restricting updates to one per year is not good science. It's convenient for bureaucratic structures but it doesn't square with reality. A JN.1 update should already be underway.
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It's like H5N1 is throwing out as many red flags as it can, trying its best to warn us. We may be sleepwalking into another pandemic, the consequences of which are unpredictable. Study paywalled unfortunately. You should be following @thijskuiken if you aren't already, BTW.
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I spend a lot of time analyzing and documenting outlier SARS-CoV-2 sequences. Recently, I’ve noticed a fascinating pattern: the repeated appearance of paired mutations in two narrow NSP12 regions >2400 nucleotides distant from each other. 1/45.
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Ran into what looks to me like the first very good candidate for deer-to-human transmission. Below is the Usher tree containing it. It's the one on the right. Before going into this seq's details, a brief description of the characteristics of deer sequences I've seen. 1/20
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At best, molnupiravir (MOV) is a useless drug we’re wasting $$ on. At worst, it could accelerate the emergence of novel variants with unpredictable characteristics. First I’ll explain why MOV is useless. Later, I’ll present evidence I’ve found that it could be dangerous. 1/.
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Could another Omicron-like event occur? Yes, it could. No one knows if or when it will happen, but there are people who have been harboring chronic infections since mid-2020 & some of these viruses involve even larger genetic jumps (saltations) than the original BA.1. 1/
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A dozen more sequences of this JN.1 + K444R + Y453F just dropped. All from Brazil, all collected in 2024. 12/13 are from the Brazilian state of Bahia, but those 12 sequences come from 11 different cities. This has the potential to be a big deal.
A JN.1 with K444R + Y453F just dropped in Brazil. JN.1 has so far exhibited Delta-like RBD stasis—perhaps, I've thought, due to its low ACE2 binding & absence of easy mutations to ⬆️ ACE2 binding. But Y453F enormously ⬆️ ACE2. Look at 444-455. We're a long way from wild-type.
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USDA/CDC still heedless of what The Great Influenza author John Barry calls the *fundamental lesson* of the 1918 pandemic:. "Those in authority must retain the public’s trust. The way to do that is to distort nothing, to put the best face on nothing, to try to manipulate no one.".
Apologies if I sound harsh in my comment about H5N1 public genomic data. It is such an important global question and now it is weeks and weeks of mention of widespread cases in mammals in the USA and data not public. Public data is the cornerstone of public health response.
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1/2 Wow. New study (full paper not yet released) finds majority of high-viral load Omicron cases are missed by almost every rapid antigen test, including the Abbott test most widely used in the US. Not good. A negative rapid test does not mean you aren't infectious.
#Omicron & #rapidtests - we have more preliminary data with retrospective testing of patient samples (all vaccine break-through). Will add to our preprint & update soon, but since it's important, see table here - confirming less reliability of negative results #SARSCoV2 #COVID19
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If you weren't already aware, BA.2.86 (Pirola) is in the US Midwest—probably the first time a major variant has been seen in the Midwest before the major US coastal cities. What's more, the sequences in Michigan & Ohio come from separate branches of BA.2.86. That means. 1/2.
Remember that BA.2.86 detection from Ohio wastewater I mentioned? The latest US patient with BA.2.86 just happens to be from the same part of Ohio (right next door). Samples were collected one day apart; could have been the same patient. 1/.
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This is a great thread. Two main points:. #1. Wastewater shows no sign of higher fecal shedding in JN.1/BA.2.86 than other variants & is thus still a very reliable proxy for infection rates. #2. JN.1 is accelerating an already existing (seasonal) Covid wave. 1/3.
Wastewater (WW) signal of SARS-CoV-2 draws an unprecedented wave in Austria. (National data from WW treatment plants covering appr. 60% pop; . This coincidences with the spread of BA.2.86* (=Pirola and its subvariants), raising two main questions: 1/n
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Incredibly honored to be featured in the Nature piece below by @maxdkozlov. I never expected anything resembling this kind of recognition, & it all still feels a bit surreal. I want to mention a few of the people whose work & generosity has been vitally important to me. 1/.
Hoping to help with the pandemic in any way they can, a motley crew of self-taught citizen scientists scour millions of SARS-CoV-2 genomes for problematic mutations — all for no pay. Meet Ryan Hisner (@LongDesertTrain), a rural school teacher from Indiana.
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@gianlucac1 @Daniel_G_Rivera @FabrizioChiodo @Doom3Gloom @ThManfredi @Di_SPACE_Lauro @ChristosArgyrop @yunlong_cao No other vaccine had anywhere near this level of success against Beta. This should be headline news, & the Soberana vaccines should be offered worldwide. What an incredible gift researchers in Cuba like @FabrizioChiodo have given to the world. Congratulations!.
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Delta's still hanging around—and packing heat, in the form of 30+ spike mutations. As w/other recent Delta singlets, this is very likely 1 chronically infected person‚ not a circulating variant. But it's a healthy reminder that the prospect of a Delta comeback always looms. 1/15
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Really happy to see our paper on SARS-CoV-2 evolution in the Omicron era out in @Nature Microbiology today. I'd normally write a thread outlining our paper, but I've not felt well for a while & can't focus well enough to do much of anything. Will try to write one later.
How #SARSCoV2 is continuing to evolve in the Omicron era, by many of the guiding lights who have so diligently tracked this virus throughout the pandemic.@NatureMicrobiol by @CorneliusRoemer @PeacockFlu @DannySheward @LongDesertTrain @siamosolocani
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The ∆69-70 pendulum is in the midst of yet another swing. What makes the alternation from ∆69-70 to S:H69+ S:V70 even more remarkable is that deletions are one-way mutations. They essentially cannot be reversed. There has never been an insertion at S:69-70 in SARS-CoV-2. 1/5
Meanwhile, Covid started one of its tricks - repeatedly losing and gaining a part of the protein spike that seems to help evade existing immunity.
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If a new variant is going to cause an increase in infections or hospitalizations, we usually don't see any indication of that until it's surpassed 50% of cases. With JN.1, some European countries are about there. But the UK, Sweden, the US, & Asia are weeks behind. 1/2
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I'm too exhausted to elaborate on this today, but here's an updated CovSpectrum graph of the ∆69-70/H69,V70 pendulum swing, complete with the major variant in each wave. This bizarre alternation remains a deep mystery, at least as far as I know. 1/3
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Before going further, I want to emphasize this sequence is a singlet. No further cases have been detected yet, & there may never be any. This could be a bolt from the blue, disappearing without a trace, as we’ve seen with other crazy sequences. 2/12.
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Greatly honored to receive this kind of praise from the likes of Dr. Topol.
Ryan is a pandemic hero, detecting and interpreting critical #SARSCoV2 mutations, the danger of molnupiravir, and so much more. His X-handle can be morphed to LongDesertThread here, an impressive one!.
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I'm still flabbergasted every time I'm reminded that in the UK and many other countries, Covid vaccination is unavailable to the majority of the population. Unjust, short-sighted, and senseless.
1. It goes without saying that the autumn COVID-19 vaccine should be offered to everyone. Doing so would reduce *demand* on healthcare systems, and this has been the case since free vaccines were restricted to certain groups.
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A BA.2.86 with S:G447C + S:G496C just dropped. Spike mutations to cysteine are rare—esp. in the receptor-binding domain (RBD). When 2 Cs show up at once, it usually means a new disulfide bond has been created. I don't think this has ever been seen in the SARS-CoV-2 RBD. 1/11
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It's long past time that we start regulating indoor air quality the same way we regulate food and water. The health effects—including detrimental cognitive effects—of poor indoor air quality are far too important to ignore.
1/ New paper in @ScienceMagazine: "Mandating Indoor Air Quality for Public Buildings". Explaining current status of indoor air quality standards (in short: bad or non-existent), the huge health benefits that would arise from them & proposing a path forward.
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Wow. Monica Gandhi is not aware that the SARS-CoV-2 receptor-binding domain is part of the spike protein. I knew her judgment was disastrous, but I had no idea her ignorance ran this deep. 1/16
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BA.2, driven to near-zero levels by BA.5, still haunt us, spawning monstrous viruses that, after vanishing for months, burst forth, gnarled & hideous, in novel antibody armor. The latest, which I found skulking around India, has 13 spike mutations. 1/28
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A 4th sequence of this lineage—now named BA.2.86— has turned up in Michigan, USA. Like the Denmark sequences, it has E554K. Still too early to forecast what kind of impact BA.2.86 will have, but with this kind of geographical spread, it doesn't seem likely to disappear quickly.
Two more sequences of this 2nd-generation BA.2 lineage just showed up in Denmark. This is the real deal. There are slight differences between the three sequences, but they are nearly identical. Below is my preliminary summary of the mutations it has on top of BA.2. 1/2
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2/6 They looked at 21 cases: 19 vaxxed, 2 unvaxxed, 17 symptomatic, 4 asymptomatic. For the symptomatic, viral loads (by PCR Ct value) were much higher on days 3-6 after symptom onset than days -1 to 2. Furthermore, many samples still had high viral loads on days 7-9.
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With the new one from London—collected Aug 13—we now have five BA.2.86 sequences from 4 different countries, none of which border each other. The two from Denmark & one from London have no travel connections. The other two we have no detailed info on re: connection to travel. 1/4.
Looks like we have 5th case of new, highly mutated Omicron variant, BA.2.86 in London UK @GSTTnhs. First identified by @shay_fleishon in Israel on 13 Aug. Our case: Hospitalised, Symptoms 13Aug, locally acquired. Sending to @KCLImmunoMicro for culture. EPI_ISL_18111770.
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6/6 CDC messaging has consistently downplayed the risk of transmission among the vaccinated, & it needs to stop. These people did everything right: they were triple-vaxxed & all tested before gathering. It didn't matter.
If vaccinated people assume they cannot be infectious, more people will be infected - including some at greater risk. That's why this isn't just stupid post hoc justification of something they are doing because they want to do it, it's dangerous. Others will follow their lead 6/n.
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How important is ORF9b? More important, I think, than almost anyone has realized. ORF9b is often neglected—it is ignored on phylogenetic trees & on GISAID sequences. I see 9 lines of evidence indicating it's a major player. But they require some background. /1
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YES! Shocking how this has gone completely under the radar. We drove a major pathogen to extinction w/a year of not-particularly-strict & inconsistently implemented NPIs & by not criss-crossing the globe in airplanes quite as much as before. Is there a lesson here? 🤔🤔 1/7.
So when do we officially celebrate B/Yamagata's demise?.
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It has 24 spike mutations compared to its nearest relative (20 AA substitutions—12 in RBD + 4 deletions). Like Omicron, this sequence is, in Covid terms, ancient. Its most recent relative disappeared about 1.5 years ago—a demon from the ancient world. I’ll call it Balrog. 3/12
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@kthalps What's amazing is that Reade's story is more clearly more credible than Ford's. It's more recent, she told three people at the time it happened who confirmed that she told them, and two people have confirmed that she was demoted for no apparent reason at the time, as she claimed.
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This means a variant with Delta-like severity & Omicron-like immune evasion is a real possibility, contrary to the Panglossian assertions of some who’ve claimed immune-evasive mutations will inevitably result in milder disease. 10/12
Furthermore, they showed that the endosomal entry pattern found in Omicron—responsible for its reduced severity & impaired ability to invade the lower respiratory tract—is mostly due to a *single mutation*— S:N969K. 13/15
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I'm not 100% sure due to uncertainties in the sequencing, but I think something remarkable has happened in JC.5.1 (an XBB.1.41 branch that has S:Q173K, L335S, R403K, K478R, S486P, & N:H300Y). There's a large ORF7a deletion that leads to ORF7a-7b fusion—and more. 1/8
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Inverse relationship between rhinovirus & SARS-CoV-2 still holding strong. Seems clear some form of viral interference is happening here. But is the causation all one way (SARS2-->RV) or does it go both ways? As someone likely suffering an RV infection right now, I'm curious 1/10
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Really sad to hear that important Long Covid studies like this are being put on hold for lack of funding.
Update: our study on #LongCovid biomarkers was put on hold after this pilot on 60 patient and controls due to lack of #funding. With @jamoulle we kept collecting/freezing samples 🙏 study https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00055-7/fulltext.
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Weird that it needs to be said, but let this be your reminder: . Getting Covid is bad. You should avoid it. We're privileged in the US to have access to the first truly updated booster—still idiotically denied to most people. The XBB.1.5 booster is good. If you can, go get it.
Covid leaves its mark on the brain!. Reposting my piece in @ConversationUS on Covid and brain health . #LongCovid.
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This has not been the primary way SARS-CoV-2 has evolved. With the notable exception of the BQ* (& partial exception of BA.2.75*) lineages, major new variants have developed during chronic infections over the course of months or years. 1/.
With a nearly unending population (esp when immune evasion is a component of the fitness advantages) the virus makes random mutations and, in concert with the human population, it continues to select whatever random mutations make the virus more fit than before. 34/.
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Recently, two seqs showed up from an infection originating around June 2020. Only a minuscule fraction of such cases are sequenced, so a non-trivial number of people have likely been infected for 4+ years. That's over 1450 days of infection. Long-term consequences: unknown.
Ugh. “No one could have predicted this”.
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US West & South approaching peak-winter Covid WW levels, with the Midwest & Northeast a few weeks behind. The release of new vaccine—early September last we heard—will be after this wave's already done its damage & schools have been in session for weeks. Worst timing possible.
Prevalence by region:. Every region increasing in wastewater levels. Both the South and West are at roughly 12 month highs. Midwest: 1 in 42 ⬆️.South: 1 in 25 ⬆️.Northest: 1 in 58 ⬆️.West: 1 in 22 ⬆️
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I think this could be said for almost anyone who deals with chronic health issues. And it takes an immense amount of mental and physical energy to fake being well, which means that being out & about for any extended period of time often leads to total exhaustion.
As a primary care doctor, I can tell you that “People with #LongCovid don’t fake being ill, they mostly fake being well”.
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Perhaps most concerning is the P681R mutation, also found in Delta and shown by @Gupta_Lab & @SystemsVirology, & others to be largely responsible for Delta’s ability to fuse cells together—called syncytia formation—a key marker for disease severity. 5/12
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Public knowledge of the H5N1 outbreak is being actively sabotaged by federal agencies. Effect of Covid has been to make public health policies around pandemics worse. Relative importance to CDC/USDA:.Agribusiness profits >>> H5N1 pandemic risk. Late capitalism at its finest.
We developed an assay for testing for H5N1 from wastewater over a year ago. (I wasn't expecting it in milk, but I figured it was going to poke up somewhere.). However, I was just on a call with the CDC and they are advising us NOT to use it. I need a drink.
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It's not clear why this is happening or what its implications are, but I'm eager to know. I spent weeks researching & writing a 🧵 on this a few months ago. All credit to @StuartTurville, who's singlehandedly brought this to the world's attention. 2/2.
I think this preprint, by @Stuartturville, is potentially one of the more important recent SARS-CoV-2 papers. It promises to unwrap some of the most mystifying aspects of Omicron surrounding cell entry, TMPRSS2 use, & reduced lung invasion/pneumonia. 1/48.
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Wow, remarkable insight here from @dgurdasani—one that she'd had long before this study came out. Yet more proof that she is one of the most incisive, reliable, & trustworthy analysts of SARS-CoV-2 matters out there.
New study in @Nature out yesterday, showing that HLA-B*15:01 and HLA-DRB1*04:01 are associated with strong T cell responses against SARS-CoV-2 & asymptomaticity- guess what other phenotype HLA-DRB1*04:01 has been associated with? Unknown fulminant hepatitis in children.🧵.
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It's early days, but the first definite BA.2.86*/XBB* recombinant, spotted by @JosetteSchoenma, is on the loose and seems to have wings. Only seven sequences right now, but it's already in Spain, France, Denmark, and the US. 1/2.
This EG.5.1.1(HK)/JN.1 recombinant has been designated and is called XDD. It has a JN.1 Spike, but 2 parts of HK at the outer parts of its genome. Only 4 samples for now, but all recent and from 3 different countries. Let's see where it goes!.
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Again, the Balrog sequence may go nowhere and affect no one. But it appears to have all the hallmarks of a variant that could sweep the world. And if this one doesn’t take flight, another chronic-infection variant will. 11/12
It's crazy that we haven't made preventing infections in the immunocompromised a #1 priority for global health. Not only is it the right thing to do morally for the sake of the immunocompromised, but it's essential for preventing dangerous new VOCs. 15/19
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Excellent piece by @EricTopol on XBB.1.5, which @JPWeiland first called attention to a couple weeks ago. Nothing is certain, but it looks like XBB.1.5 might steamroll over everything in its path in the next couple months. 1/3.
I wrote about the XBB.1.5 variant in the United States.
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Yet another reason we need to be far more forward-looking in our vaccine formulations. XBB.1.5—and other XBB+S486P variant shortly thereafter—were clearly on their way to dominance 8 months ago. Why should it take 9 months before we have a vaccine available for use? 1/3.
Why the updated, monovalent XBB.1.5 booster is needed.2 doses of the bivalent BA.5 doesn't cut it. "A second dose of the BA.5 bivalent booster is not sufficient to broaden antibody responses and to overcome immunological imprinting.".
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What's going on with ORF7b? Something unusual has occurred in ORF7b in two unrelated variants—two of the only non-XBB variants that remain competitive. They took entirely different routes to reach the same end point: a new ORF7b protein. But first a short primer on ORF7b. 1/.
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4/6 Before people start shouting about Ct values measuring dead RNA fragments, note that the researchers cultured virus from these samples, and the results mirrored those for Ct value: peak levels of live virus on days 3-6 & significant amounts of live virus on days 7-9.
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Very cool to see @Nature cover our preprint! I agree with @sarperotto. “Given the large-scale risks of this mutagen producing new variants faster, including variants that are immune evasive, I encourage public-health leaders to call for a global halt to [molnupiravir's] use.” 1/.
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Getting sick is bad for you, & getting Covid is almost certainly worse than any comparably common illness. So get your vaccinations &, as much as possible, clean the air you breathe. The latter should be a top public health priority but sadly is not. 7/7.
I’m excited to discuss our latest research on how ambient CO2 affects how long #SARSCoV2 remains infectious in air. We report that even subtle increases in CO2 affects both how long #COVIDisAirborne and transmission risk. Here’s a🧵going over the findings.
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H5N1 is no joke, even if the FDA is treating it like one.
The Louisiana Department of Health reports the patient who had been hospitalized with the first human case of highly pathogenic avian influenza (HPAI), or H5N1, in Louisiana and the U.S. has died.
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BA.2.86 data from @BenjMurrell, consistent w/study by @yunlong_cao. Antibody evasion likely no better than recent XBB. Yet BA.2.86 continues growing. Feels like there has to be some hidden aspect to BA.2.86 we haven't deciphered, though I have no idea what that might be. 1/3.
Real-time data update: we've got our first BA.2.86 (see red arrow) neutralization results. Short 🧵with much credit to @DannySheward and the rest of the team.
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. @BenjMurrell is doing the best variant growth modeling in the world, & his latest results confirm most of what we've thought: KP.3 is the fastest large variant, & its sublineage KP.3.1.1—w/the highly advantageous, glycan-creating S:∆S31—is easily the fastest in the world. 1/15.
@BenjMurrell great work now out:. Importantly it mirrors Collection 42 by @wolfeagle1989 when selcected for low CI and past 3 months and so it is a confirmation of the Covspectrum tool by @ChaoranChen_ based on another model.
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S:L455S looks like the first major improvement to BA.2.86. There will be many more. XBB* variants have had a year to develop advantageous mutations in stepwise fashion, yet baseline BA.2.86 is competitive with the best XBB* right out of the blocks. My money is on BA.2.86.
In addition to the initial 5 wastewater samples 12 additional samples collected from Bangkok in August and early September are positive (confirmed with S-gene sequencing) for BA.2.86 variant of SARS-CoV-2 with 4 sublineages with a mutation in L455S.
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