Ryan Hisner
@ryanhisner.bsky.social
Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution. LongDesertTrain on another platform.
Wow, what a shot. Beautiful bird.
November 25, 2025 at 12:15 PM
Wow, what a shot. Beautiful bird.
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
My only guess is that this G-heavy insertions are better tolerated because G's, more than any other nuc, are more likely to preserve secondary RNA structures, both because G=C bonds are stronger than A-T and because it can also form (weaker) G-T bonds.
November 23, 2025 at 10:26 PM
My only guess is that this G-heavy insertions are better tolerated because G's, more than any other nuc, are more likely to preserve secondary RNA structures, both because G=C bonds are stronger than A-T and because it can also form (weaker) G-T bonds.
I wrote some code a while back to look for clusters of any nuc mut type. They only happen for A->G. Couldn't find any similar clusters of other types of muts.
This somewhat resembles the composition of SARS-CoV-2 insertions, in which G's are vastly overrepresented. bsky.app/profile/ryan...
This somewhat resembles the composition of SARS-CoV-2 insertions, in which G's are vastly overrepresented. bsky.app/profile/ryan...
Reminder that FCS insertions are not rare or unusual & tend to resemble the OG SARS-2 FCS insert—7/9 nucs are G's in this one, consistent w/the normal G-heavy pattern of that dominates SARS-2 insertions.
1 seq uploaded today of this, which is actually in 7 sequences overall from late 2024. 1/3
1 seq uploaded today of this, which is actually in 7 sequences overall from late 2024. 1/3
November 23, 2025 at 10:26 PM
I wrote some code a while back to look for clusters of any nuc mut type. They only happen for A->G. Couldn't find any similar clusters of other types of muts.
This somewhat resembles the composition of SARS-CoV-2 insertions, in which G's are vastly overrepresented. bsky.app/profile/ryan...
This somewhat resembles the composition of SARS-CoV-2 insertions, in which G's are vastly overrepresented. bsky.app/profile/ryan...
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.
Mutations all around the FCS are incredibly convergent right now.
This one looks like a mini A->G cluster, which can sometimes be much more extensive, and which I've tried to document. I'll share a few others below.
bsky.app/profile/ryan...
This one looks like a mini A->G cluster, which can sometimes be much more extensive, and which I've tried to document. I'll share a few others below.
bsky.app/profile/ryan...
(virological wonkery alert)
Turns out there are quite a few of these A->G clusters, some even making up substantial branches in the past—an AY.74 branch had 11 A->G muts in a 380-nt stretch. 👇
These don't seem to occur for any other mut type—only A->G. 1/3
threadreaderapp.com/thread/18347...
Turns out there are quite a few of these A->G clusters, some even making up substantial branches in the past—an AY.74 branch had 11 A->G muts in a 380-nt stretch. 👇
These don't seem to occur for any other mut type—only A->G. 1/3
threadreaderapp.com/thread/18347...
November 23, 2025 at 10:04 PM
Mutations all around the FCS are incredibly convergent right now.
This one looks like a mini A->G cluster, which can sometimes be much more extensive, and which I've tried to document. I'll share a few others below.
bsky.app/profile/ryan...
This one looks like a mini A->G cluster, which can sometimes be much more extensive, and which I've tried to document. I'll share a few others below.
bsky.app/profile/ryan...
Haha, that's hilarious. Such an inquisitive mind, that one.
Let's hope this is a sign the Clown Fascist movement (which includes Bolsonaro, Erdogan, Boris Johnson, Trump, Vance, Elon Musk, Milei, etc) is in its final death throes.
Let's hope this is a sign the Clown Fascist movement (which includes Bolsonaro, Erdogan, Boris Johnson, Trump, Vance, Elon Musk, Milei, etc) is in its final death throes.
November 22, 2025 at 8:47 PM
Haha, that's hilarious. Such an inquisitive mind, that one.
Let's hope this is a sign the Clown Fascist movement (which includes Bolsonaro, Erdogan, Boris Johnson, Trump, Vance, Elon Musk, Milei, etc) is in its final death throes.
Let's hope this is a sign the Clown Fascist movement (which includes Bolsonaro, Erdogan, Boris Johnson, Trump, Vance, Elon Musk, Milei, etc) is in its final death throes.
Chronic viral infections are not innocuous. There is much evidence suggesting persistent viral reservoirs are much more common than recognized & that they cause some proportion of Long Covid. We need to take them seriously—including Cryptics. 15/end
bsky.app/profile/ryan...
bsky.app/profile/ryan...
A fascinating new preprint w/one very unexpected finding suggests, I believe, that a large proportion of Long Covid may be due to chronic infection in a particular bodily niche, which could be crucial for finding effective LC treatments. It requires some explaining. 🧵 1/33
November 22, 2025 at 7:19 PM
Chronic viral infections are not innocuous. There is much evidence suggesting persistent viral reservoirs are much more common than recognized & that they cause some proportion of Long Covid. We need to take them seriously—including Cryptics. 15/end
bsky.app/profile/ryan...
bsky.app/profile/ryan...
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
The authors do not seem aware of the existence of the related late-2024 Delta from Spain. I hope that they are able to contact the lab that sequenced the 2024 Delta & are able to follow up on the patient who provided the sample, who hopefully is still alive. 10/15
November 22, 2025 at 7:19 PM
The authors do not seem aware of the existence of the related late-2024 Delta from Spain. I hope that they are able to contact the lab that sequenced the 2024 Delta & are able to follow up on the patient who provided the sample, who hopefully is still alive. 10/15
Needless to say, a person that died in early 2023 cannot be the source of a virus from late 2024—certainly not one that had undergone extensive evolution in the intervening time period.
This is conclusive proof of Cryptic-like variant transmission. 9/15
www.ijidonline.com/article/S120...
This is conclusive proof of Cryptic-like variant transmission. 9/15
www.ijidonline.com/article/S120...
A prolonged Delta SARS-CoV-2 infection during the Omicron wave in an HIV immunosuppressed patient
We present the case of a 52-year-old man originally from the United Kingdom, resident
in Tenerife (Canary Islands, Spain), diagnosed with a deep subcutaneous abscess in
the left hemiface. After progre...
www.ijidonline.com
November 22, 2025 at 7:19 PM
Needless to say, a person that died in early 2023 cannot be the source of a virus from late 2024—certainly not one that had undergone extensive evolution in the intervening time period.
This is conclusive proof of Cryptic-like variant transmission. 9/15
www.ijidonline.com/article/S120...
This is conclusive proof of Cryptic-like variant transmission. 9/15
www.ijidonline.com/article/S120...
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
...metadata indicated that the Canary Islands seqs were from a different person than the Spain seq. But the contamination involved meant the metadata for the Spain seq could be wrong.
I continued to assume all seqs probably came from the same patient. Now we know they were not. 7/15
I continued to assume all seqs probably came from the same patient. Now we know they were not. 7/15
November 22, 2025 at 7:19 PM
...metadata indicated that the Canary Islands seqs were from a different person than the Spain seq. But the contamination involved meant the metadata for the Spain seq could be wrong.
I continued to assume all seqs probably came from the same patient. Now we know they were not. 7/15
I continued to assume all seqs probably came from the same patient. Now we know they were not. 7/15