Ryan Hisner
@ryanhisner.bsky.social
Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution. LongDesertTrain on another platform.
Reposted by Ryan Hisner
1/ Pretty amazing new results showing an unexpected benefit of mRNA vaccines. Patients who received a COVID-19 mRNA vaccine within 100 days of starting immune checkpoint inhibitor (ICI) therapy survived almost twice as long. jenndowd.substack.com/p/can-mrna-v... #episky #medsky #cancer
November 10, 2025 at 12:12 PM
1/ Pretty amazing new results showing an unexpected benefit of mRNA vaccines. Patients who received a COVID-19 mRNA vaccine within 100 days of starting immune checkpoint inhibitor (ICI) therapy survived almost twice as long. jenndowd.substack.com/p/can-mrna-v... #episky #medsky #cancer
Reposted by Ryan Hisner
Excellent thread on BA.3 from @ryanhisner.bsky.social bsky.app/profile/ryan...
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 three years, BA.3 is back.
And it is transmitting.
Who saw this coming?
1/13
After three years, BA.3 is back.
And it is transmitting.
Who saw this coming?
1/13
November 9, 2025 at 6:41 PM
Excellent thread on BA.3 from @ryanhisner.bsky.social bsky.app/profile/ryan...
Can't emphasize how damaging this is. A single non-scientist—Peter Bogner—holds all power & makes all decisions at GISAID & provides no justifications for any of them, except blatantly false ones.
He has that power because he conned rich & powerful people into giving it to him. Enough.
He has that power because he conned rich & powerful people into giving it to him. Enough.
I want to spell this out in case the implications aren't clear:
This means all public tools/webapps of GISAID data (all the ones you've been used to seeing thru the pandemic, as far as we can tell) are prohibited.
The file allowed this. Cut that - cut off all tools the public & others were using.
This means all public tools/webapps of GISAID data (all the ones you've been used to seeing thru the pandemic, as far as we can tell) are prohibited.
The file allowed this. Cut that - cut off all tools the public & others were using.
On Oct 1, 2025, GISAID informed us that they had ended updates to the flat file of SARS-CoV-2 genomic sequences and associated metadata that we had used to update Nextstrain analyses since Feb 2020. GISAID's stated rationale was that their "resources are limited". 1/5
November 10, 2025 at 2:46 AM
Can't emphasize how damaging this is. A single non-scientist—Peter Bogner—holds all power & makes all decisions at GISAID & provides no justifications for any of them, except blatantly false ones.
He has that power because he conned rich & powerful people into giving it to him. Enough.
He has that power because he conned rich & powerful people into giving it to him. Enough.
Reposted by Ryan Hisner
Continued surveillance and variant analysis is important, as highlighted by the emergence and spread of BA.3.2. Lack of data sharing by GISAID is bad news.
GISAID on providing data to @Nextstrain.org: "After consulting with our staff and advisors on the feasibility of keeping your global tree up-to-date, there was a clear consensus that continuing to generate, zip and move big files back and forth is not sustainable and a waste of resources."
🙃
🙃
Nextstrain: Interruption to GISAID-based SARS-CoV-2 sequence analyses
Nextstrain blog post from 2025-11-06; author(s): Trevor Bedford, Richard Neher and the Nextstrain team
next.nextstrain.org
November 6, 2025 at 10:14 PM
Continued surveillance and variant analysis is important, as highlighted by the emergence and spread of BA.3.2. Lack of data sharing by GISAID is bad news.
This is a total outrage and has crippled SARS-CoV-2 variant tracking and evolutionary analysis.
Updating a file and giving access to Nextstrain & Cov-Spectrum does not require extensive resources, so the official justification is a lie. There has to be an ulterior motive here.
Updating a file and giving access to Nextstrain & Cov-Spectrum does not require extensive resources, so the official justification is a lie. There has to be an ulterior motive here.
Nextstrain's daily-updated tree of SARS-CoV-2 genomes was my gateway into the world of viral phylogenetics in early 2020, and Nextstrain's beautiful interactive tree display is crucial to making usher.bio results usable. GISAID cutting off data harms global surveillance efforts. 🧵👇
On Oct 1, 2025, GISAID informed us that they had ended updates to the flat file of SARS-CoV-2 genomic sequences and associated metadata that we had used to update Nextstrain analyses since Feb 2020. GISAID's stated rationale was that their "resources are limited". 1/5
November 7, 2025 at 12:18 PM
This is a total outrage and has crippled SARS-CoV-2 variant tracking and evolutionary analysis.
Updating a file and giving access to Nextstrain & Cov-Spectrum does not require extensive resources, so the official justification is a lie. There has to be an ulterior motive here.
Updating a file and giving access to Nextstrain & Cov-Spectrum does not require extensive resources, so the official justification is a lie. There has to be an ulterior motive here.
BA.3.2 has arrived in the UK. One BA.3.2.2, collected October 5, was uploaded from Scotland today.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
November 7, 2025 at 12:10 PM
BA.3.2 has arrived in the UK. One BA.3.2.2, collected October 5, was uploaded from Scotland today.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
Same branch as recent BA.3.2.2 from Germany & Slovenia.
It has a few errors (S:ins214:ASDT is misread & ORF1a:E4388K is an artifact). Ignoring those, the one notable new mutation is N:N126K.
Reposted by Ryan Hisner
One of the greatest. I recently saw a car with a bumper sticker that said "Remember the Edmund Fitzgerald."
www.youtube.com/watch?v=FuzT...
www.youtube.com/watch?v=FuzT...
Gordon Lightfoot - Wreck Of The Edmund Fitzgerald (Official Audio)
YouTube video by Gordon Lightfoot
www.youtube.com
November 3, 2025 at 2:24 AM
One of the greatest. I recently saw a car with a bumper sticker that said "Remember the Edmund Fitzgerald."
www.youtube.com/watch?v=FuzT...
www.youtube.com/watch?v=FuzT...
Reposted by Ryan Hisner
BA.3.2 made it to New Zealand 👀
🦠Heads up. BA.3.2 has arrived in NZ
BA.3.2 detected in Aotearoa New Zealand wastewater
3.2% for the week to 5 October
BA.3.2 is not shown in the fortnight to 19 Oct. However, variants with a national percentage of < 1% are not included so BA.3.2 is likely to still be circulating
BA.3.2 detected in Aotearoa New Zealand wastewater
3.2% for the week to 5 October
BA.3.2 is not shown in the fortnight to 19 Oct. However, variants with a national percentage of < 1% are not included so BA.3.2 is likely to still be circulating
October 30, 2025 at 9:57 AM
BA.3.2 made it to New Zealand 👀
Reposted by Ryan Hisner
The cellular protease TMPRSS2 cleaves and activates the SARS-CoV-2 spike protein, priming it for membrane fusion and viral entry.
This step is essential for efficient infection of airway epithelial cells.
This step is essential for efficient infection of airway epithelial cells.
October 27, 2025 at 10:11 PM
The cellular protease TMPRSS2 cleaves and activates the SARS-CoV-2 spike protein, priming it for membrane fusion and viral entry.
This step is essential for efficient infection of airway epithelial cells.
This step is essential for efficient infection of airway epithelial cells.
First-world problem, I know, but I can't stand it when supplementary information is contained in 20 different files that have to be individually downloaded and viewed. Why not put it all in one PDF?
October 25, 2025 at 3:16 PM
First-world problem, I know, but I can't stand it when supplementary information is contained in 20 different files that have to be individually downloaded and viewed. Why not put it all in one PDF?
I can't reply to this comment, so I guess I'll quote-reply.
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
October 25, 2025 at 2:43 PM
I can't reply to this comment, so I guess I'll quote-reply.
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
The most recent molnupiravir sequences have indeed been from Australia, with the MOV stats for the most recent being pictured below.
Once again, we see strong evidence that MOV-induced mutations are being positively selected. 1/4
BA.3.2.1 still hanging out in the Netherlands. Nothing new in spike in this latest one, though 3/4 nucleotide mutations are nonsynonymous (amino acid-changing) and all are in NSP3.
One more BA.3.2.1 from netherlands
cc @snpoehlm.bsky.social @ryanhisner.bsky.social @josetteschoenma.bsky.social ( i m apparently blocked by X, likely it doesn't like intl law)
cc @snpoehlm.bsky.social @ryanhisner.bsky.social @josetteschoenma.bsky.social ( i m apparently blocked by X, likely it doesn't like intl law)
October 23, 2025 at 4:39 PM
BA.3.2.1 still hanging out in the Netherlands. Nothing new in spike in this latest one, though 3/4 nucleotide mutations are nonsynonymous (amino acid-changing) and all are in NSP3.
I beg to differ! If it's not a sequencing mistake—and it looks clean—one of these BA.3.2 has something completely novel in SARS-CoV-2 evolution: an FCS-adjacent deletion!
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
October 22, 2025 at 11:46 AM
I beg to differ! If it's not a sequencing mistake—and it looks clean—one of these BA.3.2 has something completely novel in SARS-CoV-2 evolution: an FCS-adjacent deletion!
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
One of the two QT repeats appears to have been deleted. I've never seen anything like this before. BA.3.2 is a different beast.
Due to antigenic imprinting (also called "original antigenic sin", or OAS) the antibody response is slow to turn, but turn it will, with enough repeated, UPDATED vaccinations.
Or repeated infections, I suppose, if you prefer suffering and poor health.
Or repeated infections, I suppose, if you prefer suffering and poor health.
October 21, 2025 at 12:12 PM
Due to antigenic imprinting (also called "original antigenic sin", or OAS) the antibody response is slow to turn, but turn it will, with enough repeated, UPDATED vaccinations.
Or repeated infections, I suppose, if you prefer suffering and poor health.
Or repeated infections, I suppose, if you prefer suffering and poor health.
Reminiscent of Thorstein Veblen's work. Jobs with "no taint of usefulness" are the most respectable—and the most highly paid—while manual labor or anything smacking of usefulness "is of course on a precarious footing as regards respectability"—and, it goes without saying, are poorly paid.
October 20, 2025 at 11:29 AM
Reminiscent of Thorstein Veblen's work. Jobs with "no taint of usefulness" are the most respectable—and the most highly paid—while manual labor or anything smacking of usefulness "is of course on a precarious footing as regards respectability"—and, it goes without saying, are poorly paid.
Bad. No justification, no communication, no standard procedures for making changes—just arbitrary pronouncements cutting off access to some of the most valuable resources we have.
And now NextStrain as well.
Next up, will GISAID start charging open-source community tools to have access?
That would completely shaft users who contributed to GISAID, where we never agreed to that and assumed GISAID would be good custodians of the data we contributed. They're not.
Next up, will GISAID start charging open-source community tools to have access?
That would completely shaft users who contributed to GISAID, where we never agreed to that and assumed GISAID would be good custodians of the data we contributed. They're not.
October 17, 2025 at 8:34 PM
Bad. No justification, no communication, no standard procedures for making changes—just arbitrary pronouncements cutting off access to some of the most valuable resources we have.
Reposted by Ryan Hisner
#BA32 remains detectable in a substantial fraction of Perth clinical samples for the week ending Oct 5, though total sequence and case numbers remain low.
October 16, 2025 at 5:13 PM
#BA32 remains detectable in a substantial fraction of Perth clinical samples for the week ending Oct 5, though total sequence and case numbers remain low.
Fool me once....
One of the many, many, many examples of eerie overlap between people who got Iraq WMD wrong and people who got COVID-19 "lab leak" wrong.
Not as weird as this one a few months ago, though.
Not as weird as this one a few months ago, though.
October 16, 2025 at 11:22 AM
Fool me once....
Reposted by Ryan Hisner
The final published version of this study is now available in Journal of Virology at journals.asm.org/doi/10.1128/...
Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants | Journal of Virology
This study measures how mutations to the spike of a SARS-CoV-2 variant that circulated
in early 2025 affect its function and recognition by both the polyclonal antibodies
produced by the human immune ...
journals.asm.org
October 14, 2025 at 4:22 PM
The final published version of this study is now available in Journal of Virology at journals.asm.org/doi/10.1128/...
I realized later today that I'd given the S:T124I mutation in this new sequence short shrift.
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
October 13, 2025 at 9:04 PM
I realized later today that I'd given the S:T124I mutation in this new sequence short shrift.
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
T->I amino acid changes may be the most common type, yet it's very rare (<0.01% of sequences). Why?
Because it removes a conserved glycan from N122! (Which is also conserved in SARS-CoV-1). 1/3
There's a new BA.3.2.2 from South Africa today. For the most part, there's been little substantial change in BA.3.2 over the past few months—mostly synonymous mutations & very little happening in spike.
But this new one has 3 spike mutations & looks quite interesting. 1/6
But this new one has 3 spike mutations & looks quite interesting. 1/6
October 13, 2025 at 12:04 PM
There's a new BA.3.2.2 from South Africa today. For the most part, there's been little substantial change in BA.3.2 over the past few months—mostly synonymous mutations & very little happening in spike.
But this new one has 3 spike mutations & looks quite interesting. 1/6
But this new one has 3 spike mutations & looks quite interesting. 1/6
Reposted by Ryan Hisner
Finally, CoV-Spectrum is meeting trees 🌳 – this week, we released a new feature to browse the SARS-CoV-2 UShER tree on CoV-Spectrum. With the new feature, you can see a subtree of your variant of interest. 1/4
August 28, 2025 at 7:41 AM
Finally, CoV-Spectrum is meeting trees 🌳 – this week, we released a new feature to browse the SARS-CoV-2 UShER tree on CoV-Spectrum. With the new feature, you can see a subtree of your variant of interest. 1/4
Reposted by Ryan Hisner
I just updated our cryptic lineage dashboard if anyone is interested.
Viewer warning: this site contains a ton of actual data that really long persistent COVID infections are still occurring.
1/
dholab.github.io/public_viz/0...
Viewer warning: this site contains a ton of actual data that really long persistent COVID infections are still occurring.
1/
dholab.github.io/public_viz/0...
SARS-CoV-2 Cryptic Lineage Visualizations
dholab.github.io
October 3, 2025 at 9:51 PM
I just updated our cryptic lineage dashboard if anyone is interested.
Viewer warning: this site contains a ton of actual data that really long persistent COVID infections are still occurring.
1/
dholab.github.io/public_viz/0...
Viewer warning: this site contains a ton of actual data that really long persistent COVID infections are still occurring.
1/
dholab.github.io/public_viz/0...
"The Great Pumpkin"—@siamosolocani.bsky.social's apt nickname for BA.3.2—has now shown up in New South Wales, Australia, for the first time.
Together with its continued presence in clinical samples and wastewater in Western Australia, this confirms real community BA.3.2 transmission in AUS.
1/3
Together with its continued presence in clinical samples and wastewater in Western Australia, this confirms real community BA.3.2 transmission in AUS.
1/3
New South Wales has uploaded their samples to GISAID.
They have also found a BA.3.2 for the first time!
Several were found before in Western Australia.
They have also found a BA.3.2 for the first time!
Several were found before in Western Australia.
September 27, 2025 at 12:40 PM
"The Great Pumpkin"—@siamosolocani.bsky.social's apt nickname for BA.3.2—has now shown up in New South Wales, Australia, for the first time.
Together with its continued presence in clinical samples and wastewater in Western Australia, this confirms real community BA.3.2 transmission in AUS.
1/3
Together with its continued presence in clinical samples and wastewater in Western Australia, this confirms real community BA.3.2 transmission in AUS.
1/3
Attenuation of the SARS-2 furin-cleavage site (FCS) continues apace. It's beginning to look as if some form of FCS-weakening mutation might well become fixed in the near future. Collectively, they are at ~12% globally—a totally unprecedented level—& rising quickly. 1/4
September 25, 2025 at 11:57 PM
Attenuation of the SARS-2 furin-cleavage site (FCS) continues apace. It's beginning to look as if some form of FCS-weakening mutation might well become fixed in the near future. Collectively, they are at ~12% globally—a totally unprecedented level—& rising quickly. 1/4