Ryan Hisner
@ryanhisner.bsky.social
Teacher. Learner. Investigating mysteries of SARS-CoV-2 evolution. LongDesertTrain on another platform.
Also, Buttigieg is a McKinsey guy—a corporate elite through and through.
Very similar to Obama and Bill Clinton; he's very smart and a fabulous talker, but he'll never set foot on a picket line or push a policy that threatens Capital.
www.currentaffairs.org/news/2019/03...
Very similar to Obama and Bill Clinton; he's very smart and a fabulous talker, but he'll never set foot on a picket line or push a policy that threatens Capital.
www.currentaffairs.org/news/2019/03...
All About Pete
Only accept politicians who have proved they actually care about people other than themselves…
www.currentaffairs.org
January 19, 2026 at 1:41 AM
Also, Buttigieg is a McKinsey guy—a corporate elite through and through.
Very similar to Obama and Bill Clinton; he's very smart and a fabulous talker, but he'll never set foot on a picket line or push a policy that threatens Capital.
www.currentaffairs.org/news/2019/03...
Very similar to Obama and Bill Clinton; he's very smart and a fabulous talker, but he'll never set foot on a picket line or push a policy that threatens Capital.
www.currentaffairs.org/news/2019/03...
...in places where the nationalization of local politics and gerrymandering has made it impossible for anyone without an "R" next to their name to crack 40%.
January 19, 2026 at 1:36 AM
...in places where the nationalization of local politics and gerrymandering has made it impossible for anyone without an "R" next to their name to crack 40%.
AOC is the face and future of the party, and this is a very good thing. Zohran is a juggernaut, & getting Graham Platner into the Senate would be huge. Maybe more than anything we need hundreds of grassroots campaigns driven by volunteers at the local & state levels, but this is a heavy lift...
January 19, 2026 at 1:36 AM
AOC is the face and future of the party, and this is a very good thing. Zohran is a juggernaut, & getting Graham Platner into the Senate would be huge. Maybe more than anything we need hundreds of grassroots campaigns driven by volunteers at the local & state levels, but this is a heavy lift...
The idea that any NHP study or one without an NL63-infected control group "does not count" is just bizarre to me.
If you're bar is incontrovertible proof, then sure, they "don't count." But that kind of certainty is scarce in biology & totally dismissing these studies seems close-minded.
If you're bar is incontrovertible proof, then sure, they "don't count." But that kind of certainty is scarce in biology & totally dismissing these studies seems close-minded.
January 18, 2026 at 5:48 PM
The idea that any NHP study or one without an NL63-infected control group "does not count" is just bizarre to me.
If you're bar is incontrovertible proof, then sure, they "don't count." But that kind of certainty is scarce in biology & totally dismissing these studies seems close-minded.
If you're bar is incontrovertible proof, then sure, they "don't count." But that kind of certainty is scarce in biology & totally dismissing these studies seems close-minded.
Together w/the macaque study showing persistent infection of alveolar macrophages in BAL samples & the preprint where those w/LC had Ab responses consistent w/persistent antigen & w/the deep-lung mutation pattern, I think the possibility of persistent deep-lung infection is worth taking seriously.
January 18, 2026 at 5:48 PM
Together w/the macaque study showing persistent infection of alveolar macrophages in BAL samples & the preprint where those w/LC had Ab responses consistent w/persistent antigen & w/the deep-lung mutation pattern, I think the possibility of persistent deep-lung infection is worth taking seriously.
One SARS-CoV-2 variant (B.1.616) displayed the same mutational pattern as BAL-sample chronic-infection sequences, and it also resulted in repeatedly negative NP-swab PCR tests but severe lung pathology and positive BAL-sample tests.
bsky.app/profile/ryan...
bsky.app/profile/ryan...
One candidate for the most severe Covid variant is B.1.616. It was very difficult to detect w/nasopharyngeal-swab PCR tests, though it showed up readily on BAL samples. Had an adjusted hazard ratio for severe outcomes of 4.0 relative to Alpha/Gamma/Beta (mostly Alpha) in the same time period. 3/4
January 18, 2026 at 5:48 PM
One SARS-CoV-2 variant (B.1.616) displayed the same mutational pattern as BAL-sample chronic-infection sequences, and it also resulted in repeatedly negative NP-swab PCR tests but severe lung pathology and positive BAL-sample tests.
bsky.app/profile/ryan...
bsky.app/profile/ryan...
No, there is no Euclidean proof here. There is enough evidence to take the possibility seriously though.
There are >15 case studies documenting repeated negative NP-swab PCR tests followed by positive BAL samples in chronically infected symptomatic patients.
There are >15 case studies documenting repeated negative NP-swab PCR tests followed by positive BAL samples in chronically infected symptomatic patients.
January 18, 2026 at 5:48 PM
No, there is no Euclidean proof here. There is enough evidence to take the possibility seriously though.
There are >15 case studies documenting repeated negative NP-swab PCR tests followed by positive BAL samples in chronically infected symptomatic patients.
There are >15 case studies documenting repeated negative NP-swab PCR tests followed by positive BAL samples in chronically infected symptomatic patients.
"All else does not count" seems pretty dismissive.
I'm not making any claims with certainty here; I'm pointing out that evidence from multiple sources suggests the possibility that persistent LRT infection could explain some proportion of Long Covid.
I'm not making any claims with certainty here; I'm pointing out that evidence from multiple sources suggests the possibility that persistent LRT infection could explain some proportion of Long Covid.
January 18, 2026 at 5:48 PM
"All else does not count" seems pretty dismissive.
I'm not making any claims with certainty here; I'm pointing out that evidence from multiple sources suggests the possibility that persistent LRT infection could explain some proportion of Long Covid.
I'm not making any claims with certainty here; I'm pointing out that evidence from multiple sources suggests the possibility that persistent LRT infection could explain some proportion of Long Covid.
No comparison to influenza in the macaque study (due to limited numbers of macaques/resources I imagine), but elsewhere experiments with precision cut human lung slices found that SARS-CoV-2 productively infects alveolar macrophages during acute infection while IAV does not.
January 18, 2026 at 5:11 PM
No comparison to influenza in the macaque study (due to limited numbers of macaques/resources I imagine), but elsewhere experiments with precision cut human lung slices found that SARS-CoV-2 productively infects alveolar macrophages during acute infection while IAV does not.
There were healthy controls, i.e. uninfected macaques. When they say "compared to HC," this is what they are referring to.
January 18, 2026 at 4:43 PM
There were healthy controls, i.e. uninfected macaques. When they say "compared to HC," this is what they are referring to.
I've read that paper, which is really interesting. Unclear to me that is says anything one way or another about the possibility of persistent infection of the deep lung or alveolar macrophages.
January 18, 2026 at 4:29 PM
I've read that paper, which is really interesting. Unclear to me that is says anything one way or another about the possibility of persistent infection of the deep lung or alveolar macrophages.
They found evidence of infectious virus in BAL samples from in 21/25 macques. I thought this was pretty clear. Not clear to me what you think is dishonest about any of this.
bsky.app/profile/ryan...
bsky.app/profile/ryan...
They found that RNA- and antigen-positive BAL samples contained infectious virus that productively replicated in alveolar macrophages in cell culture. Even a few of the RNA- and antigen-negative samples showed evidence of productive replication (84% showed increasing levels of spike over time).
January 18, 2026 at 4:21 PM
They found evidence of infectious virus in BAL samples from in 21/25 macques. I thought this was pretty clear. Not clear to me what you think is dishonest about any of this.
bsky.app/profile/ryan...
bsky.app/profile/ryan...
That study does not appear to have anything to do with the possibility of persistent SARS-CoV-2 LRT infection or infection of alveolar macrophages.
January 18, 2026 at 4:17 PM
That study does not appear to have anything to do with the possibility of persistent SARS-CoV-2 LRT infection or infection of alveolar macrophages.
I was pointing out that my very next post directly addressed your objection that viral RNA/antigen ≠ infectious virus.
Not sure how your post from 2023 has any relevance to this, unless it's just a reminder that you once read the paper but have now forgotten they found infectious virus.
Not sure how your post from 2023 has any relevance to this, unless it's just a reminder that you once read the paper but have now forgotten they found infectious virus.
January 18, 2026 at 4:12 PM
I was pointing out that my very next post directly addressed your objection that viral RNA/antigen ≠ infectious virus.
Not sure how your post from 2023 has any relevance to this, unless it's just a reminder that you once read the paper but have now forgotten they found infectious virus.
Not sure how your post from 2023 has any relevance to this, unless it's just a reminder that you once read the paper but have now forgotten they found infectious virus.
Is there a better model than experimental infection of non-human primates for this? It's not possible to do the same study in humans. Even taking BAL samples from patients not suffering severely from acute symptoms is ethically impermissible.
January 18, 2026 at 4:05 PM
Is there a better model than experimental infection of non-human primates for this? It's not possible to do the same study in humans. Even taking BAL samples from patients not suffering severely from acute symptoms is ethically impermissible.
They found that RNA- and antigen-positive BAL samples contained infectious virus that productively replicated in alveolar macrophages in cell culture. Even a few of the RNA- and antigen-negative samples showed evidence of productive replication (84% showed increasing levels of spike over time).
January 18, 2026 at 3:51 PM
Here's a link to that paper. There are several others that support productive infection of alveolar macrophages, though they focus on acute infection. I'd do a longer, more comprehensive thread including info from those, but I'm too exhausted & can't think right now.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells - Nature Immunology
Huot et al. show that interferon-γ (IFN-γ) regulates the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar macrophages from cynomolgus macaques up to 18 mo...
www.nature.com
January 18, 2026 at 3:33 PM
Here's a link to that paper. There are several others that support productive infection of alveolar macrophages, though they focus on acute infection. I'd do a longer, more comprehensive thread including info from those, but I'm too exhausted & can't think right now.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
The near absence of RBD spike muts in chronic-infection BAL-sample sequences fits neatly w/the cell-cell spread they found in alveolar macs—as do some other aspects. Less clear why this might incr E antibodies, but the extraordinarily high rate of E mutations in BAL seqs hints at a connection.
January 18, 2026 at 3:33 PM
The near absence of RBD spike muts in chronic-infection BAL-sample sequences fits neatly w/the cell-cell spread they found in alveolar macs—as do some other aspects. Less clear why this might incr E antibodies, but the extraordinarily high rate of E mutations in BAL seqs hints at a connection.
There are many other really interesting findings in that paper—including an intriguing counterbalancing act of IFN-γ & MHC-E in alveolar macs that could help explain persistence (IFN-γ associated w/viral control but also increased MHC-E expression, which inhibits NK cytotoxicity).
January 18, 2026 at 3:33 PM
There are many other really interesting findings in that paper—including an intriguing counterbalancing act of IFN-γ & MHC-E in alveolar macs that could help explain persistence (IFN-γ associated w/viral control but also increased MHC-E expression, which inhibits NK cytotoxicity).
They found that RNA- and antigen-positive BAL samples contained infectious virus that productively replicated in alveolar macrophages in cell culture. Even a few of the RNA- and antigen-negative samples showed evidence of productive replication (84% showed increasing levels of spike over time).
January 18, 2026 at 3:33 PM
They found that RNA- and antigen-positive BAL samples contained infectious virus that productively replicated in alveolar macrophages in cell culture. Even a few of the RNA- and antigen-negative samples showed evidence of productive replication (84% showed increasing levels of spike over time).
...they had chronic infection in the alveolar compartment. A majority of macaques tested + for viral RNA (68%) or antigen (80%). The typical explanation for this is that these are fragments of lingering viral material and that no viable virus remains. But...
January 18, 2026 at 3:33 PM
...they had chronic infection in the alveolar compartment. A majority of macaques tested + for viral RNA (68%) or antigen (80%). The typical explanation for this is that these are fragments of lingering viral material and that no viable virus remains. But...
It's also consistent w/the findings of a non-human primate experiment in which macaques completely cleared all viral RNA from from their nasal tract & trachea within 3 weeks—like the typical human—but who nonetheless had elevated inflammatory markers for >1 yr (duration of study). It turned out...
January 18, 2026 at 3:33 PM
It's also consistent w/the findings of a non-human primate experiment in which macaques completely cleared all viral RNA from from their nasal tract & trachea within 3 weeks—like the typical human—but who nonetheless had elevated inflammatory markers for >1 yr (duration of study). It turned out...
This isn't a new preprint; it came out about 4 months ago, when I wrote a 🧵 on it. Not sure why there's a sudden resurgence in interest.
I find it extremely interesting because the findings are consistent with a pattern I've discovered in chronic deep-lung infections.
bsky.app/profile/ryan...
I find it extremely interesting because the findings are consistent with a pattern I've discovered in chronic deep-lung infections.
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
January 18, 2026 at 3:33 PM
This isn't a new preprint; it came out about 4 months ago, when I wrote a 🧵 on it. Not sure why there's a sudden resurgence in interest.
I find it extremely interesting because the findings are consistent with a pattern I've discovered in chronic deep-lung infections.
bsky.app/profile/ryan...
I find it extremely interesting because the findings are consistent with a pattern I've discovered in chronic deep-lung infections.
bsky.app/profile/ryan...
From Scott's "Two Cheers for Anarchism," a short collection of essays & one of my favorite books, which I hand out to anyone that might be interested as often as possible.
January 17, 2026 at 3:31 PM
From Scott's "Two Cheers for Anarchism," a short collection of essays & one of my favorite books, which I hand out to anyone that might be interested as often as possible.