Ryan Hisner

Ryan Hisner

@ryanhisner.bsky.social

Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution. LongDesertTrain on another platform.

9.1K followers422 following2.3K posts

Pinned

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.bsky.social just spied a weird spike in NYC wastewater—& it's the same one! 1/14

Solid Evidence@solidevidence.bsky.social

This is kind of weird. A new cryptic showed up in two different NYC sewersheds this month. Low coverage. RBD piece is: 403K-405N-408S-417N-435S-439N-445P-446T-450D-452K-455S-456L. Also a deletion at 621-622. 1/

18/22 sequences from New Brunswick, Canada, uploaded today are PJ.2.1. First time we've seen this level of dominance in any region. Four of the PJ.2.1 have S:A475V, a major class-1 antibody escape mutation that has emerged several times independently in PJ.2.1. bsky.app/profile/ryan...

Ryan Hisner@ryanhisner.bsky.social

As outlined previously, Yunlong Cao's team has demonstrated in previous studies that A475V is a major escape mutation for antibodies that PJ.2.1 is extremely vulnerable to. bsky.app/profile/ryan...

Massively undercovered story given the serious pandemic risk this H5N1 outbreak in a US mink farm poses. Utterly insane that the public health reaction here is to shrug our shoulders and essentially do nothing. Yet another way the US is a menace to the rest of the world.

Ryan Hisner reposted

This! I feel like @gquirk96.bsky.social and I've been shouting into the wind. Don't assume that original antigenic sin is why we don't make antibodies against certain drifted epitopes. Some are just inherently not antigenic, irrespective of prior immunity. www.nature.com/articles/s41...

nature.comIntrinsic immunogenicity is a major determinant of type-specific responses in SARS-CoV-2 infections - Nature ImmunologyBhattacharya and colleagues assess the impact of antigenic imprinting using samples from mRNA vaccinated or unvaccinated individuals primarily infected with the SARS-CoV-2 variants Delta and Omicron B...
Bloom lab@jbloomlab.bsky.social

In new study, we show that SARS-CoV-2 has evolved decreased inherent antigenicity in humans, as quantified by a ~3-fold decrease in the number of naïve human B cells that can bind the spike RBD. doi.org/10.64898/202...

Ryan Hisner reposted

We predicted that JN.1-like sweeps would end, with multiple variants co-circulating instead. Now PJ.2.1 has entered the mix. What happens next? Indicate your prediction by liking the corresponding reply below. 👇

Two PJ.2.1/RC.5 recombinants were uploaded from NYC yesterday—breakpoint in the spike RBM, between S:456-S:477. Likely originated in Ontario, where RC.5 + S:I478T + S:S943G is mostly found (as @siamosolocani.bsky.social pointed out) & is therefore circulating. RC.5 is a NB.1.8.1 descendant.

PJ.2.1 is a fast-growing saltation variant descended from KP.3.1.1-->MC.10.1.7, which last circulated in early 2025 before reappearing this year, almost certainly after extensive intrahost evolution in a chronically infected patient.

A recombinant this soon in the PJ.2.1 spike signals to me that— unlike in BA.3.2—the SD1/2 & S2 mutations (T547K, ∆622-623, ∆N641, V642I, ins643PMA, Q644E, Q675K, ins791P, D839K, A958S,D1146G, I1169F, V1264L) in PJ.2.1 are not compensatory for its NTD/RBD mutations, and therefore aren't essential.

3/7 sequences uploaded by Western Australia today are PJ.2.1, including 3/4 of the most recently collected sequences. PJ.2.1 now seems to be well established and growing in Australia and New Zealand.

Ryan Hisner reposted

We analyzed cell entry and antibody-mediated neutralization of the emerging saltation variant PJ.2.1. Check out our preprint below! #PJ21 1/ We found that PJ.2.1 shows increased ACE2 binding and enhanced entry into cells expressing low levels of ACE2.

66 airport SARS-CoV-2 sequences from incoming travelers were uploaded today, collected Sept 21-30, and 26 (39.4%) were PJ.2.1. 20/30 (66.7%) sequences from Latin American travelers were PJ.2.1. Seems likely that PJ.2.1 is rapidly sweeping across the entire Western hemisphere.

6/24 (25%) travel sequences from Europe were PJ.2.1: Two from the UK and one each from Belgium, Italy, Spain, and Turkey. There were no PJ.2.1 sequences from Africa (0/4) or Asia (0/8). Very few mutations in these sequences, likely a sign of rapid PJ.2.1 growth.

Previous post on PJ.2.1 for background info. bsky.app/profile/ryan...

Ryan Hisner@ryanhisner.bsky.social

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

3/33 sequences from New Zealand uploaded today are PJ.2.1. All three very recently collected though, so that 3/11 of the most recent sequences (since Sept 26) are PJ.2.1, meaning it could already be significantly higher than 10% prevalence. PJ.2.1 growth seems to be accelerating of late.

Stefan Pöhlmann@snpoehlm.bsky.social

PJ.2.1 has reached New Zealand 🇳🇿 and Israel 🇮🇱. New Zealand: 3 sequences, all collected in late September Israel: 1 sequence, collected in late August #PJ21

PJ.2.1 is growing fast. Nothing's certain—PJ.2.1 could be like BA.3.2, confined to a certain segment of the population—but it looks to me right now like PJ.2.1 could sweep, at least in Western countries. Japan, SE Asia, & China harder to predict as the immune landscape is very different there.

Ryan Hisner reposted

🦠 COVID-19 and chronic infections – Also comment about not being able to get own PCR test results. Perhaps that’s a USA thing? I know I’d be wanting to look mine up! 😀

Ryan Hisner@ryanhisner.bsky.social

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

Ryan Hisner reposted

Fascinating thread from Ryan. Below is an explainer of what is likely going on with these v different looking variants, except in this new PJ case the chronically infected person seems to be continually transmitting infections that establish themselves in others. theconversation.com/the-emergenc...

theconversation.comThe emergence of JN.1 is an evolutionary ‘step change’ in the COVID pandemic. Why is this significant?The JN.1 variant has become dominant in Australia and around the world, causing large waves of infections. Here’s what we know about it so far – and why it’s so important.
Ryan Hisner@ryanhisner.bsky.social

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

Just to add some detail to the PJ.2.1 picture outlined in the thread below, here's a Venn diagram (modeled on Cov-Spectrum's) of the four major PJ branches' amino acid mutations (excluding all shared, inherited MC.10.1.7 mutations).

Ryan Hisner@ryanhisner.bsky.social

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

View full thread

And as long as that's the case—and I think it will be the case as long as the evidence, however convincing, remains indirect—there's basically no chance there will be concerted public health efforts to identify and treat chronic infections.

And suppose we find out that PJ.2.1 was circulating among immunosenescent individuals in some relatively isolated nursing home in Ontario—and that its circulation could've been prevented with efficient ventilation and air filtration? I think this would be an important revelation for public health.

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

View full thread

Second, it seems this person is continuing to shed diverse variants, some of which have the potential to spread and possibly cause an increase in Covid cases worldwide. Not an ideal situation for society, so there's a global public health interest here, in my opinion.

Third, figuring out how saltation variants like these evolve and spread is the first step toward figuring out how to prevent them. I think people who study Covid are pretty well in agreement that these variants arise in chronic infections, but the wider public & most doctors know nothing about it.

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

View full thread

First, there's almost certainly at least 1 person suffering a chronic infection without knowing it—sequences are never shared w/patients, AFAIK, which I consider unethical, but which seems to be standard practice. (I called the company that did my + PCR test asking for info & was stonewalled.)

There are tons of case studies of people clearing chronic infections with multi-drug treatment (usually Paxlovid + remdesivir), so someone's quality of life or even their life could be at stake.

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

View full thread

While I think the most likely explanation is that each of these diverse PJ* variants evolved in & were/are being transmitted from the same person, it's also possible that a small # of closely connected, relatively isolated individuals w/chronic infections are the source.

I think it's important to figure out which of these scenarios (or perhaps something entirely different) has given rise to the various PJ* variants, for a number of reasons.

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

View full thread

And obviously, these did not evolve stepwise during circulation, which would require dozens & dozens of repeated reversions & repeated evolution of identical mutations, deletions, & insertions. To me, there's only one plausible explanation for this: intrahost evolution. bsky.app/profile/ryan...

Ryan Hisner@ryanhisner.bsky.social

The tree for this whole branch is completely unlike what you typically see. I suspect that all these branches derive from a single chronically infected individual who has transmitted diverse variants numerous times—quite possibly what happened in the original BA.1/2/3 Omicron outbreak as well. 3/5

I previously outlined the reasons why I think these lineages are a result of intrahost evolution during chronic infection—most likely in the same individual—in the sub-thread below. bsky.app/profile/ryan...

Ryan Hisner@ryanhisner.bsky.social

Several reasons. First, the mutations are very chronic-like—like nothing we see in circulating branches. 2nd, While it's maybe hard to tell from the image, the tree makes no sense from a stepwise evolution perspective. There are multiple reversions and distant branches share uncommon mutations.

Large upload from Ontario yesterday, providing some striking revelations about the evolution of PJ.2.1. First, there is yet another strikingly divergent branch of PJ.2.1. This isn't one variant: it's four. More and more, this resembles the emergence of BA.1/2/3. What is happening? 1/

These different PJ-tree branches are NOT simply recombinants of two different genotypes. There are no clear breakpoints in any of them. Each branch shares numerous mutations with every other branch and has many unique mutations of its own, all scattered across the genome.

I wonder if this is due to Japan's more successful avoidance of pre-Omicron infection—emphasizing ventilation, masking, & avoiding crowded indoor spaces, which undoubtedly saved countless lives—making their infection history more similar to that of young children (which BA.3.2 is known to prey on).

Stefan Pöhlmann@snpoehlm.bsky.social

New sequences from Saitama and Yamanashi, Japan 🇯🇵, collected from June through September: over 70% are BA.3.2 Looking at September alone, nearly 60% are BA.3.2 As others have noted, the frequency of BA.3.2 in Japan remains unexpectedly high. #BA32

But the major flaw in that hypothesis is the near-total absence (as far as we can tell) of BA.3.2 in China. Given that China almost entirely avoided pre-Omicron infections, they ought to be particularly susceptible to BA.3.2, as Yunlong Cao & co. predicted. bsky.app/profile/ryan...

Ryan Hisner@ryanhisner.bsky.social

Furthermore, the results from this preprint suggest BA.3.2 should have great success in China, with its weakly imprinted population. But we've yet to see a single BA.3.2 sequence from China. (Caveat: extremely low sequencing in China of late). 5/6 bsky.app/profile/ryan...

Since Aug 31, 12.8% (10/78) airport surveillance seqs from international travelers to the US have been PJ.2.1. 45% (9/20) from Latin American travelers in that period are PJ.2.1: 4 from Cuba & 1 each from Chile, Colombia, the DR, Ecuador, & Guatemala. PJ.2.1 is the fastest variant in the world now.

Ryan Hisner@ryanhisner.bsky.social

Update on PJ.2.1, the saltation variant originating in Ontario & found in wastewater in ~10 US states. 11/75 sequences today from New York are PJ.2.1. Eight of 11 sequences are identical, with the three others differing by 1 nuc mut. Such limited diversity typically indicates rapid spread. 1/5

Ryan Hisner reposted

Replying to @sourcecontrol.bsky.social

Dass GISAID über die Rechtsform eines deutschen eingetragenen Vereins (e.V.) läuft, führt in der internationalen Wissenschaftsgemeinschaft zu heftiger Kritik Ein e.V. unterliegt in 🇩🇪 im Vergleich zu Aktiengesellschaften oder großen Stiftungen kaum Veröffentlichungspflichten! bsky.app/profile/ryan...

Ryan Hisner@ryanhisner.bsky.social

Researchers still muzzle themselves for they fear losing GISAID access. I know professional scientists who privately despise GISAID/Bogner but say nothing publicly because they fear the wrath of Bogner—an absurd state of affairs. 11/

3rd independent branch of PJ.2.1 with S:A475V appeared today. This seems to be a winning mutation in PJ.2.1, which has excess ACE2 affinity to burn. However, all 3 branches are singlets so far, so it hasn't caught fire or anything. PJ.2.1 at 25% in Maryland in very recent samples, as Fede says 👇

Federico Gueli@siamosolocani.bsky.social

New Batch from Maryland PJ.2.1 at 25% 8/32 or 5/19 looking at samples colected after Sept 15 (included) First place where we see PJ.2.1 as leading variant

Also saw a PJ.2.1 in Spain with S:N334K, a big Ab-evading mutation according to the @jbloomlab.bsky.social KP.3.1.1 DMS stats—nearly as evasive as XFG's S:N487D. However, that one also had a bizarre deletion in N (∆203-208) that ought to ~abolish N phosphorylation, likely highly deleterious.

Had no idea how common dengue has become in Florida. Per the CDC, >1000 non-travel-associated US dengue cases in 2026, mostly Florida. A guy I ran cross-country with in high school lost a teenage daughter to dengue last year. Can't believe this isn't big news. www.microbe.tv/twiv/twiv-13...

microbe.tvTWiV 1362: Clinical Update with Dr. Daniel GriffinIn his weekly clinical update, Daniel Griffin and Vincent Racaniello continue their ongoing exasperation over 5 deaths in Pennsylvania associated with measles infections, the absurdity of RFK Jr.’s st...

Prediction market and sports gambling companies are the new tobacco companies. How long will we allow their depredations continue to destroy lives? Tobacco advertising was banned decades ago. Why are gambling ads permitted to stain every sports broadcast? It's sickening.

Darren Dahly@statsepi.bsky.social

Zero value created. Zero social benefit. Pure transfer of wealth, preying on the vulnerable. I don't understand how anyone involved sleeps at night.