Ryan Hisner
@ryanhisner.bsky.social
Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution. LongDesertTrain on another platform.
Note that here we see two more instances of the "unnatural" CGG triplet, allegedly forbidden except in cases of lab manipulation.
I guess Omicron's synonymous A27259C mutation (in ORF6) is also evidence for evil-scientist treachery.
I guess Omicron's synonymous A27259C mutation (in ORF6) is also evidence for evil-scientist treachery.
November 24, 2025 at 4:01 AM
Note that here we see two more instances of the "unnatural" CGG triplet, allegedly forbidden except in cases of lab manipulation.
I guess Omicron's synonymous A27259C mutation (in ORF6) is also evidence for evil-scientist treachery.
I guess Omicron's synonymous A27259C mutation (in ORF6) is also evidence for evil-scientist treachery.
Another fun little ORF3a A->G cluster in two Canadian LP.8.1.1.
ORF3a: K16G, E19G, K21G, I35M, I37M, I47V
A25431G, A25438G, A25439G, A25443G, A25448G, A25453G, A25454G, A25497G, A25503G, A25506G, A25531G
ORF3a: K16G, E19G, K21G, I35M, I37M, I47V
A25431G, A25438G, A25439G, A25443G, A25448G, A25453G, A25454G, A25497G, A25503G, A25506G, A25531G
November 23, 2025 at 10:35 PM
Another fun little ORF3a A->G cluster in two Canadian LP.8.1.1.
ORF3a: K16G, E19G, K21G, I35M, I37M, I47V
A25431G, A25438G, A25439G, A25443G, A25448G, A25453G, A25454G, A25497G, A25503G, A25506G, A25531G
ORF3a: K16G, E19G, K21G, I35M, I37M, I47V
A25431G, A25438G, A25439G, A25443G, A25448G, A25453G, A25454G, A25497G, A25503G, A25506G, A25531G
The most extensive A->G cluster of all that is definitely real (multiple US states & labs) is this BA.1.
16 A->G muts in across 315-nt in ORF6 & ORF7a.
A27375G, A27363G, A27398G, A27449G, A27452G, A27486G, A27492G, A27562G, A27571G,
A27620G, A27624G, A27636G, A27647G, A27663G, A27669G, A27675G
16 A->G muts in across 315-nt in ORF6 & ORF7a.
A27375G, A27363G, A27398G, A27449G, A27452G, A27486G, A27492G, A27562G, A27571G,
A27620G, A27624G, A27636G, A27647G, A27663G, A27669G, A27675G
November 23, 2025 at 10:32 PM
The most extensive A->G cluster of all that is definitely real (multiple US states & labs) is this BA.1.
16 A->G muts in across 315-nt in ORF6 & ORF7a.
A27375G, A27363G, A27398G, A27449G, A27452G, A27486G, A27492G, A27562G, A27571G,
A27620G, A27624G, A27636G, A27647G, A27663G, A27669G, A27675G
16 A->G muts in across 315-nt in ORF6 & ORF7a.
A27375G, A27363G, A27398G, A27449G, A27452G, A27486G, A27492G, A27562G, A27571G,
A27620G, A27624G, A27636G, A27647G, A27663G, A27669G, A27675G
One last A->G cluster which, in terms of sheer density, is probably the most impressive. AY.25.1 branch detected in four different countries had six A->G mutations in a 25-nt stretch of ORF3a.
A25426G , A25432G , A25442G, A25443G, A25449G, A25450G
A25426G , A25432G , A25442G, A25443G, A25449G, A25450G
November 23, 2025 at 10:29 PM
One last A->G cluster which, in terms of sheer density, is probably the most impressive. AY.25.1 branch detected in four different countries had six A->G mutations in a 25-nt stretch of ORF3a.
A25426G , A25432G , A25442G, A25443G, A25449G, A25450G
A25426G , A25432G , A25442G, A25443G, A25449G, A25450G
Typo in one of my posts above: the K679G A->G cluster pictured there was from New York, not Hawaii. This is the somewhat similar one that was from Hawaii.
November 23, 2025 at 10:26 PM
Typo in one of my posts above: the K679G A->G cluster pictured there was from New York, not Hawaii. This is the somewhat similar one that was from Hawaii.
This actually is the largest (in terms of sequences) A->G cluster I've found. Eight A->G mutations in a 350-sequece branch of Beta in ORF8, which seems like a good place for this sort of thing since its main importance seems to lie in its role in secondary RNA structure.
November 23, 2025 at 10:18 PM
This actually is the largest (in terms of sequences) A->G cluster I've found. Eight A->G mutations in a 350-sequece branch of Beta in ORF8, which seems like a good place for this sort of thing since its main importance seems to lie in its role in secondary RNA structure.
This one is really interesting because it included two A->G mutations in the BA.1 insertion, which very rarely mutated. It was detected in multiple countries and by different labs.
Eight A->G mutations within a 150-nt stretch.
Eight A->G mutations within a 150-nt stretch.
November 23, 2025 at 10:15 PM
This one is really interesting because it included two A->G mutations in the BA.1 insertion, which very rarely mutated. It was detected in multiple countries and by different labs.
Eight A->G mutations within a 150-nt stretch.
Eight A->G mutations within a 150-nt stretch.
I tried to map out the location of the A->G muts in the secondary RNA structure for that one. Not sure if it's very enlightening though.
November 23, 2025 at 10:10 PM
I tried to map out the location of the A->G muts in the secondary RNA structure for that one. Not sure if it's very enlightening though.
Oftentimes the A->G clusters are in singlets, but a number of them have transmitted and been detected by different labs. I think this is the most widely spread one. 11 A->G nuc muts in a 375-nt stretch—all apparently occurring simultaneously on the same phylogenetic branch.
November 23, 2025 at 10:08 PM
Oftentimes the A->G clusters are in singlets, but a number of them have transmitted and been detected by different labs. I think this is the most widely spread one. 11 A->G nuc muts in a 375-nt stretch—all apparently occurring simultaneously on the same phylogenetic branch.
Here's an XEC from Hawaii that also had Q675R and K679G, as well as five other A->G mutations within about 250 nt of each other.
November 23, 2025 at 10:06 PM
Here's an XEC from Hawaii that also had Q675R and K679G, as well as five other A->G mutations within about 250 nt of each other.
See, e.g., the Ohio Cryptic, which had ORF3a:H182D. At its peak, this single person shed as much virus as the entire sewershed at the peak of the BA.1 wave—by far the most intense Covid wave in the US.
Then it suddenly vanished & never reappeared. 14/15
Then it suddenly vanished & never reappeared. 14/15
November 22, 2025 at 7:19 PM
See, e.g., the Ohio Cryptic, which had ORF3a:H182D. At its peak, this single person shed as much virus as the entire sewershed at the peak of the BA.1 wave—by far the most intense Covid wave in the US.
Then it suddenly vanished & never reappeared. 14/15
Then it suddenly vanished & never reappeared. 14/15
As @solidevidence.bsky.social has noted, ORF3a:H182D is often found in Cryptic WW lineages. We do not know the outcome of these infections, but the fact that these lineages often suddenly & mysteriously disappear—immediately after excreting insane amounts of virus—is not encouraging. 13/15
November 22, 2025 at 7:19 PM
As @solidevidence.bsky.social has noted, ORF3a:H182D is often found in Cryptic WW lineages. We do not know the outcome of these infections, but the fact that these lineages often suddenly & mysteriously disappear—immediately after excreting insane amounts of virus—is not encouraging. 13/15
There have only been ~15 known patients infected with viruses with ORF3a:H182D. We know that four of those patients died. The outcome of the rest is unknown.
The other Cryptic variant that transmitted & killed a young child (see 👆) also had ORF3a:H182D. 12/15
The other Cryptic variant that transmitted & killed a young child (see 👆) also had ORF3a:H182D. 12/15
November 22, 2025 at 7:19 PM
There have only been ~15 known patients infected with viruses with ORF3a:H182D. We know that four of those patients died. The outcome of the rest is unknown.
The other Cryptic variant that transmitted & killed a young child (see 👆) also had ORF3a:H182D. 12/15
The other Cryptic variant that transmitted & killed a young child (see 👆) also had ORF3a:H182D. 12/15
In addition to confirming transmission of a Cryptic variant, this study confirms another trend I've noted before: Viruses with ORF3a:H182D have a disturbing habit of killing their host. 11/15
November 22, 2025 at 7:19 PM
In addition to confirming transmission of a Cryptic variant, this study confirms another trend I've noted before: Viruses with ORF3a:H182D have a disturbing habit of killing their host. 11/15
How could we possibly know this without any certain metadata from the Spain Delta?
A case study for the Canary Islands pt was just published. 1st sentence:
"Here, we describe a fatal, prolonged Delta SARS-CoV-2 infection lasting 55 days...in a severely immunosuppressed HIV patient." 8/15
A case study for the Canary Islands pt was just published. 1st sentence:
"Here, we describe a fatal, prolonged Delta SARS-CoV-2 infection lasting 55 days...in a severely immunosuppressed HIV patient." 8/15
November 22, 2025 at 7:19 PM
How could we possibly know this without any certain metadata from the Spain Delta?
A case study for the Canary Islands pt was just published. 1st sentence:
"Here, we describe a fatal, prolonged Delta SARS-CoV-2 infection lasting 55 days...in a severely immunosuppressed HIV patient." 8/15
A case study for the Canary Islands pt was just published. 1st sentence:
"Here, we describe a fatal, prolonged Delta SARS-CoV-2 infection lasting 55 days...in a severely immunosuppressed HIV patient." 8/15
I figured it would always remain a total mystery, but months later came a surprise: 11 sequences collected in late 2022 & early 2023 at the Canary Islands & very clearly related to the 2024 Spanish Delta were uploaded. The Canary Island sequences were all from the same patient. Intriguingly... 6/15
November 22, 2025 at 7:19 PM
I figured it would always remain a total mystery, but months later came a surprise: 11 sequences collected in late 2022 & early 2023 at the Canary Islands & very clearly related to the 2024 Spanish Delta were uploaded. The Canary Island sequences were all from the same patient. Intriguingly... 6/15
I had zero doubt this Delta sequence came from a real virus, but there were problems. There were a ton of reversions late in the genome as well as a few JN.1 mutations.
You see this in recombination, but there were no clear breakpoints here, so that part seemed unreal. 4/15
You see this in recombination, but there were no clear breakpoints here, so that part seemed unreal. 4/15
November 22, 2025 at 7:19 PM
I had zero doubt this Delta sequence came from a real virus, but there were problems. There were a ton of reversions late in the genome as well as a few JN.1 mutations.
You see this in recombination, but there were no clear breakpoints here, so that part seemed unreal. 4/15
You see this in recombination, but there were no clear breakpoints here, so that part seemed unreal. 4/15
The most recent example requires some background. In late 2024, a spectacularly mutated Delta appeared in Spain with 40 new spike mutations and numerous Cryptic markers.
Normally, I would write a thread about such a remarkable sequence, but there were some issues with the sequence... 3/15
Normally, I would write a thread about such a remarkable sequence, but there were some issues with the sequence... 3/15
November 22, 2025 at 7:19 PM
The most recent example requires some background. In late 2024, a spectacularly mutated Delta appeared in Spain with 40 new spike mutations and numerous Cryptic markers.
Normally, I would write a thread about such a remarkable sequence, but there were some issues with the sequence... 3/15
Normally, I would write a thread about such a remarkable sequence, but there were some issues with the sequence... 3/15
The first instance involved a small cluster of sequences that hospitalized several people & resulted in the death of a young child in early 2022. Unfortunately, no case study was published & attempts to contact the lab involved were unsuccessful. More on this one later. 2/15
November 22, 2025 at 7:19 PM
The first instance involved a small cluster of sequences that hospitalized several people & resulted in the death of a young child in early 2022. Unfortunately, no case study was published & attempts to contact the lab involved were unsuccessful. More on this one later. 2/15
Fascinating one. Massive increase in ACE2 binding with S:I358F according to @jbloomlab.bsky.social DMS—among the highest of any viable mutation. Seems to inhibit entry and increases vulnerability to antibodies, but with a colossal ACE2 boost like that, it could easily find other Ab-evading muts.
November 19, 2025 at 1:50 AM
Fascinating one. Massive increase in ACE2 binding with S:I358F according to @jbloomlab.bsky.social DMS—among the highest of any viable mutation. Seems to inhibit entry and increases vulnerability to antibodies, but with a colossal ACE2 boost like that, it could easily find other Ab-evading muts.
As @siamosolocani.bsky.social has pointed out, these two sequences from Sydney are related to previous BA.3.2 collected there, indicating local spread, not a separate introduction.
Collection dates in the NSW upload ranged from Sept 20-Nov 2, w/the BA.3.2 being among the more recent: Oct 20 & 27.
Collection dates in the NSW upload ranged from Sept 20-Nov 2, w/the BA.3.2 being among the more recent: Oct 20 & 27.
November 17, 2025 at 12:03 PM
As @siamosolocani.bsky.social has pointed out, these two sequences from Sydney are related to previous BA.3.2 collected there, indicating local spread, not a separate introduction.
Collection dates in the NSW upload ranged from Sept 20-Nov 2, w/the BA.3.2 being among the more recent: Oct 20 & 27.
Collection dates in the NSW upload ranged from Sept 20-Nov 2, w/the BA.3.2 being among the more recent: Oct 20 & 27.
...like CovSpectrum & @kgandersen.bsky.social's Outbreak, has been senselessly denied access to essential SARS-CoV-2 genomic data by the pathological liar, con man, & non-scientist who tyrannically runs GISAID. This is a travesty and a stain on science and shouldn't be tolerated any longer.
3/3
3/3
November 13, 2025 at 12:23 AM
...like CovSpectrum & @kgandersen.bsky.social's Outbreak, has been senselessly denied access to essential SARS-CoV-2 genomic data by the pathological liar, con man, & non-scientist who tyrannically runs GISAID. This is a travesty and a stain on science and shouldn't be tolerated any longer.
3/3
3/3
BA.3.2.2 nearly 50% of recent Western Australia sequences—perhaps on a path to dominance there?
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
November 13, 2025 at 12:23 AM
BA.3.2.2 nearly 50% of recent Western Australia sequences—perhaps on a path to dominance there?
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
In this latest batch, there's another furin-cleavage site (FCS)-adjacent ∆QT sequence. It's very closely related to the first one, so there's now no doubt that the deletion is real. 1/3
Bossman. Perfect companion piece to the Big Bossman action figure. Such a close resemblance too.
November 12, 2025 at 2:57 AM
Bossman. Perfect companion piece to the Big Bossman action figure. Such a close resemblance too.
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.