As mentioned in the "footprint" vs transmission section, the authors show evidence in favor of active transmission (and so acute infection) for the Gamma and Alpha clusters, enough that I was on team transmission by the time I finished the post. In particular, if it was chronic infection or just leftover lymph node RNA then there should be more Gamma outside of the cluster.
However, Peter provides rather good pushback on that conclusion in the comment below. Also, I noticed after posting that the 7 successful viral cultures were all associated with Delta sequences, which is definitely a reason to interpret the study more cautiously than I probably did.
Sep 13, 2022·edited Sep 13, 2022Liked by Brian Mowrey
As someone who grew up in farmer area, but now lives in a deep forest and has been hiking and hunting (pictures only though) in remote areas from childhood, I was fascinated by this deer reservoir first I heard of it over a year ago. I was as it didn't make sense.
First these deer are not herd deer, unlike Elk. The females form sometimes small groups of 2 or 3, but never large packs. They are also fairy stationary. I've had the same female having young in my yard for three years in a row now. In our neighborhood we hence even have names for some of the deer with expressive features, that is how stationary they are.
So it is unlikely this is deer to deer transmission driven. Also the idea that I as a hunter or photographer would infect a deer is ludicrous. I've seen suggestions that they transmit through their own poop or nose-rubbing, but the quantity of infected deer seem to be too high.
(The fact that the researchers never thought this was strange shows these are city folk. :-) )
The most plausible explanation I heard discussed is poop spraying. Unknown to most people is that many American states use wastewater to spray lands. This spraying goes on for hours and creates large clouds of mist. Also realize that unlike the mountain states (Montana etc) and the West Coast most states don't have true vast virgin forests but large mixed use areas where agriculture and forested areas meet. Deer hence frequently roam around farmland getting exposed to these poop-mists. Time of deer activity and time of spraying also focusses around evenings.
So my guess is that these are not primarily deer-to-deer, but just poop sprayed infected. Various studies showed that they could easily not just detect but easily get live samples from wastewater.
Then indeed as pointed out, the virus remains likely just in the lymph node for a long time.
Of course I could be wrong, and there is truly an animal reservoir. That would be very troublesum, but my bet is it is just that - poop spraying.
Very excellent comments (this and your other one below) - but, your model (like Ethical Skeptic's) depends on ruling out long distance airborne transmission and spooky quantum genomic behavior. This is a problem because influenza has demonstrated long distance airborne transmission and spooky quantum genetic behavior forever: how does the entire world come down with symptoms so quickly (even before modern ic / rail / air transportation), and how is it the thing that is egg-passaged or sequenced on one end of the earth matches the other in terms of the ferret antibody response and/or spike protein (HA) genetic code?
The answer can't be "poop spraying" because again this has been the case with flu since horse and carriage times. I have my own fancy model - but the more important point is that it's not necessary for hosts to rub noses or share a pen to spread a respiratory virus.
Still, it's a very good counter-theory in of itself. The thing I would note as in my reply to A Edward is that the phylogenetic evidence in the Gamma and Alpha clusters was convincing in favor of sustained transmission in a reservoir. I even added a note in the footnotes regarding the possibility of a lab leak of Gamma into deer - that still doesn't match the genetic evidence. And, as I also discuss, there's the problem of why there wasn't any Gamma "footprint" outside of the cluster - how is that consistent with poop spraying? Essentially I started writing my review in favor of a lymph node footprint theory only to find the guts of the paper to contradict rather than substantiate it, so I switched teams.
So one way or another you have this Gamma genome that is apparently from a single recorded human origin and has been passaged around "something," and has shown up in the deer lymph nodes. So it still works as a "proof of concept" of the animal reservoir trope.
I need to overthink the Gamma footprint, but I think these are two independent chess games, as should be evaluated separately.
First though, I may have loved the word 'poop spraying' too much, and put you on the wrong foot. I'm not talking about the traditional spraying of solids on farmland. Not only does that only happen a few times a year, but that doesn't really happen anymore in modern agriculture.
We still spread cattle manure of course, but that is purely waste management and typically done on lands that are already oversaturated with nitrogen anyway, and not infrequent lands that is not even be used to grow crops. It is just that proper disposal is more expensive. Hence, farmers would have no interest in spraying human waste, even if there wasn't a huge set of regulations around that. Waste companies at the minimum would have to pay farmers to spray it, else they would never take it. There is some compost waste management from human waste (e.g. LOOP), that ends up on farmlands, but that is often sterilized or otherwise "treated". There is lots of stuff wrong there, as the waste-industry as a whole is crooked, but I don't think that is a major source of transmission, if at all.
What I mean is the spraying of the waste water. Waste water spraying is daily and often lasts for hours. That is fairly new principle. Fairly new as in a few decades old. And it is also only done in a few states at a large scale. Hence an easy disproval of my theory would show if deer in states like Orgeron or Montana away from the handful of farm areas there would have covid-19 too. I dare make a bet they don't, and it is isolated to the farm-forest states.
Further, just as spooky remote actions in Quantum Mechanics are a myth (the most common misunderstanding of the Copenhagen interpretation in fact - there are no spooky interactions at long distances), I remain unconvinced that exists for flu too. Evidence in flu strongly suggests that it are travel patterns. It is just that it is common and transmits through both aerosols and dirty hands., that it goes fast and silent.
But let's say I'm wrong! How would the kinetics work? Why would small flu-aerosols not disperse and dry up? Physics works against this theory. But even more so, how would one get large amounts of aerosols in the air? In fact, aren't the only two possible sources of human spray, in fact agriculture poop-water spraying and the waste water plants itself, as these also spray continuously? I don't imagine an open-air rock concert with even thousands of jumping people produce enough aerosols ...
So the only discussions seems to be, how far does poop spraying aerosols/droplet-mists go? Based on my experience, a few dozen feet. That is how far the green vegetation is around farmlands vs the dried up vegetation. That is also where deer love to hang out. Plus to dismay of farmers they also like to hang out on the farmland itself of course, so they would get sprayed on directly!
But let's say they do flow further; that seems more an extension of my theory than a disproval?
The consequence would be that covid transmission around waste plants would also be larger and miles around such a waste plant one would see large increases of covid transmission in urban zones. I don't think we've seen any evidence this is the case?
Nevertheless, a great discussion as always on this site!
I very much appreciate concrete knowledge of any human industry, as these things are never efficiently put on paper / internet; but waste management is an especially delicious topic. You also reminded me that one element of the unfinished fiction project that kicked off my thinking about viruses many years ago was deer as an agricultural bioterrorism vector...
It is a bit difficult to reply concisely to your affirmation of host-to-host transmission without being sure if you mean in advance of outbreaks or during outbreaks. So here is a very non-concise attempt.
During outbreaks, transmission might sometimes be apparent on the interregional level (as in 1948; but not so much 1918) but cannot account for intra-regional patterns. As Shope wrote, "Johnson supported his contention about the spread of [1789 outbreak] influenza [as being spread by a quality in the air] by citing examples from the pandemic of 1782, in which he felt transmission by contact did not play the essential role. He stated, 'Influenza appeared at London between the 12th and 18th, at Oxford in the third week, and at Edinburgh on the 20th day of May.' He doubted that the disease could have been transferred to these three cities in such rapid succession 'by things imbued with the contagion or by persons labouring under the complaint.'" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951634/)
Explaining such fast transmission in an era of horse and foot travel requires, at the least, that we dispense with any conclusions about limited viability based on physics / lab culture-based experiments (esp. as these also leave out bacterial interactions which might help boost viability of viruses in vivo; we are still in the dark ages of knowing what really goes on here). Somehow the virus can travel long distances in the air. (This makes other examples easier to explain, like Pacific island outbreaks in 1918).
On the other hand, if you meant that the virus spreads in a "seeding" manner at the speed of human-to-human transmission, only for outbreaks to appear after the fact, then that is the classic counter-model to a perfect "quality of the air" (long distance transmission) model.
Because human flu lacks genetic diversity (whereas it is abundant in avian flu, where there is no immune pressure; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC372859/ p 167), even during antigenic "drift" years there is a total die-out of previous phenotypes and a new global ascendance of usually just one spike / HA protein mutant. So the seeding model is actually carrying an incredible load here - 1 Drift mutants must possess a fitness advantage even in a context of sub-clinical infection 2 Everyone on Earth who gets the flu every year must have a chain of contact to the original person who made the new HA mutant 3 There must be some other dynamic that explains the rise in symptomatic illness that doesn't have to do with immune escape / fitness, because the virus already collected those gains during the seeding phase.
Perfect long distance airborne transition restores the link between immune escape / fitness and symptomatic expression, accommodates seeding in drift years and doesn't require it in new subtype/shift years. However, I do think it is weak in terms of plausibility for viability and persistence of the virus in off season.
Thus, in essence, the virus behaves both like it is a species (as it does in avian flu, where there is more genetic diversity) in that it seems to rely on widespread subclinical infection and a single organism (no genetic diversity) in that an immune escape phenotype displaces all other genomes every year. SARS-CoV-2 appears to behave the same way, but this may be an artifact of continued lab release.
Sep 14, 2022·edited Sep 14, 2022Liked by Brian Mowrey
Thank you for the concise explanation.
And yes, I'm suggesting the seeding model. Humans seed in one area and from there it rapidly spreads inter-community. Hence in the 1782 likely the seeding happened earlier than Johnson thinks it did. It was already spreading, similar just like in 2020 when we noticed the outbreaks, we later learned there was already community spread for weeks.
I'd imagine with modern sequencing we would more easily proof prove or disprove these models, as long distance spread would have different patterns of micro-mutations than the seeding model.
(Although in modern times, with cars etc you'd also get more cross spread, and you'd be more sensitive in quality of contact tracing.)
My main concern is long distance travel would indeed break with most ideas about limited viability based on physics. Hence I'm not ready to depart from there. But then again, most of this field is just a few decades old, so I'm sure we humans have lot to learn.
The issue that every person must have a link to the 'new HA mutant 3' is curious, indeed. But doesn't covid kind of proves it? Summer 2019 there was nothing. A year later it was everywhere. Omicron repeated that. So, the seed model worked in the initial spread, even if there is a role in long distance later on!
The more pressing problem IMHO is why e.g. Omiron could push out Delta despite plenty of non-immune hosts remaining. Similar like the total die out of old flu phenotypes, although that is helped by existing hosts being immune. But I think these are explained by the same two things.
A first level there is the observation that mutations always occur and there *must* be a die-out. No copies are perfect. The more a virus allows drift, to more quicker it inherently will die out replacing itself. This explains why flu strains never remain. For covid this is less of a factor as mutations seems to be less effective in immune escape due to the fact covid targets a receptor and not a generic aminoacid and hence has less flexibility in effective mutations.
So the 2nd and remaining question is why do some types prevail and others not? I personally suspect this is just an artifact of math/randomness. Most infected people don't infect anybody outside their household and hence being a dead end. Just a few infect multiple. So average R-values are misleading as most have R=0 but a few have large R's. Hence randomness causes most sub-strains to inherently die out. The ones with either an evolutionary benefit or a biochemical likelihood to exist, will prevail.
See it as a game of musical chair dance game. Every turn a few seats are taken away. But then every 3rd turn all seats are placed back due to natual immunity fading. The new seats will be taken by clones of the remaining players. Just mathematically the one that has the largest presence after the 2nd turn, will have more chance to take the chairs that are put back. That is how Deta died out, and how some flu drift directions die out.
But I admit none of all this is a perfect explanation, so there is certainly room for alternatives or compliments. It may not be one or the other, but some interacting factors too.
RE SARS-CoV-2, I regretted comparing the spread dynamics after I posted. SARS-CoV-2 hasn't seemed to defy person-to-person transmission on an interregional level, even if I think it does do so intraregionally.
RE Delta dying out, along with BA.1 pushing back BA.2 when it got a foothold first (as in US, UK, Israel), and then BA.1 dying out, p 172 of "Evolution and Ecology" (my second link in last reply) gives what I think is still the best theory, which that escape mutants raise the antiviral T Cell background response and this crowds out non-escape mutants, leading to the mutant becoming fixed.
RE receptors, the residues that directly bind sialic acid are usually described as highly conserved. In fact I forget whether there are multiple motifs across subtypes or types at all, other than host-specific galactose linkage. Also, this conserved loop is non-immunogenic (https://www.nature.com/articles/289373a0). But the sites around are highly immunogenic and labile, though again seem to be conserved when there is no immune pressure (as in H1N1 swine, and in avian HAs, p164 of the second link in my previous reply).
But in general your seeding + musical chairs model is probably what I would lean toward if I didn't believe in long distance transmission. Even so, there is a problem with the model in that it suggests the chairs are prohibited from replenishing when there are "more than one" previous players still remaining. There's still a bit of "spooky ex machina" built into the model by this assumption, the model just covers it under a bit of cloth.
I should go ahead and posit my current working theory, which is that we frequently have persistent last-season viral replication still going on well into the next season, which is both tolerated in terms of not being totally cleared but suppressed in terms of not being symptomatic. A novel HA/NA mutant does in fact spread at the rate of apparent transmission, implying long distance transmission. These genes, despite being carried in what would otherwise be "dead" flu virions, land in cells that currently contain slowly-replicating residual virus, like a song transmitting into radios that are already turned on, waiting to play it. For this reason the HA and NA genes behave like a single organism while other other six flu "internal" genes show genetic diversity in humans - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC110138/ - Just what determines the fitness of new HA/NA mutants does still seem to be immune escape, at least in my current view.
This theory isn't strictly meant to explain observed fast transmission during "pandemics" - which frequently result in replacement of the internal genes as well, or might usually occur when there are no more residual infections to piggy-back off. But it does offer a spin-off model where new avian (re-)crossovers seed the population of the Earth under similar tolerance / suppression, until once again a mutant HA / NA gene combo disseminates at observed transmission speeds, implying long distance airborne transmission. This "first" mutant HA / NA might be more related to host tropism than immune escape.
Still I am not so wedded to this model as to think it is required for long-distance transmission in a nonsegmented genome, as with SARS-CoV-2.
I did come up with one (1) deer-related pun title for this review, but I forgot it when I temporarily shelved the post. It isn't the same pressure to perform when I only use puns for sub-titles now, haha.
So...on a serious note....what is the long term ramification here?
If deer "may serve as a reservoir for variant SARS-CoV-2 strains that no longer circulate in the human population," then how likely is it that said SARS-CoV-2 strains will spillback into the human population on a large scale (e.g. like the delta wave), especially since they once circulated in humans?
And, in light of the Ig4 tolerance study, if the B cells of the 2X+ vaccinated are programmed to make Ig4 antibodies when the immune system is challenged by SARS-CoV-2, then wouldn't such a spillover be "like paper and fire" (to quote JC Mellencamp)?
In other words, if 60-70% of the population have their immune systems primed to tolerate SARS-CoV-2 rather than fight it, it seems to me that these deer reservoirs could be the source for a real pandemic ala GVB (albeit a different mechanism than his model).
I would suggest that what is probably transpiring is the end of Silence of the Lambs crane shot. Wild-animal-crossover-Delta, or even BA.1, melting into a sea of oblivious tourists, with no yet-apparent mortality impact.
IgG4 tolerance may prolong viral clearance even while antibodies still nullify viremia and severe outcomes. However, pulmonary vasculature might get a lot more gooey from retro-crossover-Delta vs. the non-TMPRSS2-requiring Omicron strains, in which case severe outcomes would not be as well-prevented. Result: Ominous crane shot, check back next sequel...
Sep 13, 2022·edited Sep 13, 2022Liked by Brian Mowrey
Of course all that assumes deer to human back transmission.
Other than Kid-petting and other zoos or so I don't see how, other than incidental. Unlike with large chicken and pork factories where human workers daily have an opportunity to cross-infect like woth flu, this doesn't look like a common route. And the occasional back jump would hit a wall of large human immunity.
The only thing that would be worrying IMHO is, if inside deer we would get unique mutations, and these mutations would not hurt its capabilities to infect humans back and would cause higher lethality and escape immunity from older strains. But that are a lot of if's. And that would require deer-to-deer transmission, to cultivate these mutations and I'm not convinced on that too.
In that sense the Mink farms were more worrisome. This deer-reservoir seems more a puzzle than a worry to me at this point.
Ah, true, he does mention it - related to fecal transmission if I remember correctly. There's a lot of good insights in that thesis, but I'm not sure it's more compelling than Gamma crossing over in spring via airborne route and then being maintained in deer.
It's likely that many wildlife biologist or conservationists have tagged animals in the wild that they monitor and so maybe at some point they decided to check on Bambi to evaluate for things such as deer ticks and other pathogens and happened to find out that they had COVID.
Good point - I didn't think to look into that. Wildlife disease surveillance / control always strikes me as very "op-y" to begin with. Like, is this expensive compared to airborne rabies vaccine scattering, etc... The money's definitely out there, but it is weird not to list a grant
Tingling noted. Perhaps it was all accomplished with after-hours work, hence the long time to get it to preprint. That's doubtful but kind of endearing to imagine.
Don't see any obvious clues in the supplemental material metadata. Pdf has Martins' name / email as the author (as opposed to Joey@CIA.gov etc).
Incredible! Does it mean that deer are chronically or contunually infected? If 21% test positive then likely some deer just keep carrying the virus?
As mentioned in the "footprint" vs transmission section, the authors show evidence in favor of active transmission (and so acute infection) for the Gamma and Alpha clusters, enough that I was on team transmission by the time I finished the post. In particular, if it was chronic infection or just leftover lymph node RNA then there should be more Gamma outside of the cluster.
However, Peter provides rather good pushback on that conclusion in the comment below. Also, I noticed after posting that the 7 successful viral cultures were all associated with Delta sequences, which is definitely a reason to interpret the study more cautiously than I probably did.
As someone who grew up in farmer area, but now lives in a deep forest and has been hiking and hunting (pictures only though) in remote areas from childhood, I was fascinated by this deer reservoir first I heard of it over a year ago. I was as it didn't make sense.
First these deer are not herd deer, unlike Elk. The females form sometimes small groups of 2 or 3, but never large packs. They are also fairy stationary. I've had the same female having young in my yard for three years in a row now. In our neighborhood we hence even have names for some of the deer with expressive features, that is how stationary they are.
So it is unlikely this is deer to deer transmission driven. Also the idea that I as a hunter or photographer would infect a deer is ludicrous. I've seen suggestions that they transmit through their own poop or nose-rubbing, but the quantity of infected deer seem to be too high.
(The fact that the researchers never thought this was strange shows these are city folk. :-) )
The most plausible explanation I heard discussed is poop spraying. Unknown to most people is that many American states use wastewater to spray lands. This spraying goes on for hours and creates large clouds of mist. Also realize that unlike the mountain states (Montana etc) and the West Coast most states don't have true vast virgin forests but large mixed use areas where agriculture and forested areas meet. Deer hence frequently roam around farmland getting exposed to these poop-mists. Time of deer activity and time of spraying also focusses around evenings.
So my guess is that these are not primarily deer-to-deer, but just poop sprayed infected. Various studies showed that they could easily not just detect but easily get live samples from wastewater.
Then indeed as pointed out, the virus remains likely just in the lymph node for a long time.
Of course I could be wrong, and there is truly an animal reservoir. That would be very troublesum, but my bet is it is just that - poop spraying.
Very excellent comments (this and your other one below) - but, your model (like Ethical Skeptic's) depends on ruling out long distance airborne transmission and spooky quantum genomic behavior. This is a problem because influenza has demonstrated long distance airborne transmission and spooky quantum genetic behavior forever: how does the entire world come down with symptoms so quickly (even before modern ic / rail / air transportation), and how is it the thing that is egg-passaged or sequenced on one end of the earth matches the other in terms of the ferret antibody response and/or spike protein (HA) genetic code?
The answer can't be "poop spraying" because again this has been the case with flu since horse and carriage times. I have my own fancy model - but the more important point is that it's not necessary for hosts to rub noses or share a pen to spread a respiratory virus.
Still, it's a very good counter-theory in of itself. The thing I would note as in my reply to A Edward is that the phylogenetic evidence in the Gamma and Alpha clusters was convincing in favor of sustained transmission in a reservoir. I even added a note in the footnotes regarding the possibility of a lab leak of Gamma into deer - that still doesn't match the genetic evidence. And, as I also discuss, there's the problem of why there wasn't any Gamma "footprint" outside of the cluster - how is that consistent with poop spraying? Essentially I started writing my review in favor of a lymph node footprint theory only to find the guts of the paper to contradict rather than substantiate it, so I switched teams.
So one way or another you have this Gamma genome that is apparently from a single recorded human origin and has been passaged around "something," and has shown up in the deer lymph nodes. So it still works as a "proof of concept" of the animal reservoir trope.
I need to overthink the Gamma footprint, but I think these are two independent chess games, as should be evaluated separately.
First though, I may have loved the word 'poop spraying' too much, and put you on the wrong foot. I'm not talking about the traditional spraying of solids on farmland. Not only does that only happen a few times a year, but that doesn't really happen anymore in modern agriculture.
We still spread cattle manure of course, but that is purely waste management and typically done on lands that are already oversaturated with nitrogen anyway, and not infrequent lands that is not even be used to grow crops. It is just that proper disposal is more expensive. Hence, farmers would have no interest in spraying human waste, even if there wasn't a huge set of regulations around that. Waste companies at the minimum would have to pay farmers to spray it, else they would never take it. There is some compost waste management from human waste (e.g. LOOP), that ends up on farmlands, but that is often sterilized or otherwise "treated". There is lots of stuff wrong there, as the waste-industry as a whole is crooked, but I don't think that is a major source of transmission, if at all.
What I mean is the spraying of the waste water. Waste water spraying is daily and often lasts for hours. That is fairly new principle. Fairly new as in a few decades old. And it is also only done in a few states at a large scale. Hence an easy disproval of my theory would show if deer in states like Orgeron or Montana away from the handful of farm areas there would have covid-19 too. I dare make a bet they don't, and it is isolated to the farm-forest states.
Further, just as spooky remote actions in Quantum Mechanics are a myth (the most common misunderstanding of the Copenhagen interpretation in fact - there are no spooky interactions at long distances), I remain unconvinced that exists for flu too. Evidence in flu strongly suggests that it are travel patterns. It is just that it is common and transmits through both aerosols and dirty hands., that it goes fast and silent.
But let's say I'm wrong! How would the kinetics work? Why would small flu-aerosols not disperse and dry up? Physics works against this theory. But even more so, how would one get large amounts of aerosols in the air? In fact, aren't the only two possible sources of human spray, in fact agriculture poop-water spraying and the waste water plants itself, as these also spray continuously? I don't imagine an open-air rock concert with even thousands of jumping people produce enough aerosols ...
So the only discussions seems to be, how far does poop spraying aerosols/droplet-mists go? Based on my experience, a few dozen feet. That is how far the green vegetation is around farmlands vs the dried up vegetation. That is also where deer love to hang out. Plus to dismay of farmers they also like to hang out on the farmland itself of course, so they would get sprayed on directly!
But let's say they do flow further; that seems more an extension of my theory than a disproval?
The consequence would be that covid transmission around waste plants would also be larger and miles around such a waste plant one would see large increases of covid transmission in urban zones. I don't think we've seen any evidence this is the case?
Nevertheless, a great discussion as always on this site!
I very much appreciate concrete knowledge of any human industry, as these things are never efficiently put on paper / internet; but waste management is an especially delicious topic. You also reminded me that one element of the unfinished fiction project that kicked off my thinking about viruses many years ago was deer as an agricultural bioterrorism vector...
It is a bit difficult to reply concisely to your affirmation of host-to-host transmission without being sure if you mean in advance of outbreaks or during outbreaks. So here is a very non-concise attempt.
During outbreaks, transmission might sometimes be apparent on the interregional level (as in 1948; but not so much 1918) but cannot account for intra-regional patterns. As Shope wrote, "Johnson supported his contention about the spread of [1789 outbreak] influenza [as being spread by a quality in the air] by citing examples from the pandemic of 1782, in which he felt transmission by contact did not play the essential role. He stated, 'Influenza appeared at London between the 12th and 18th, at Oxford in the third week, and at Edinburgh on the 20th day of May.' He doubted that the disease could have been transferred to these three cities in such rapid succession 'by things imbued with the contagion or by persons labouring under the complaint.'" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951634/)
Explaining such fast transmission in an era of horse and foot travel requires, at the least, that we dispense with any conclusions about limited viability based on physics / lab culture-based experiments (esp. as these also leave out bacterial interactions which might help boost viability of viruses in vivo; we are still in the dark ages of knowing what really goes on here). Somehow the virus can travel long distances in the air. (This makes other examples easier to explain, like Pacific island outbreaks in 1918).
On the other hand, if you meant that the virus spreads in a "seeding" manner at the speed of human-to-human transmission, only for outbreaks to appear after the fact, then that is the classic counter-model to a perfect "quality of the air" (long distance transmission) model.
Because human flu lacks genetic diversity (whereas it is abundant in avian flu, where there is no immune pressure; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC372859/ p 167), even during antigenic "drift" years there is a total die-out of previous phenotypes and a new global ascendance of usually just one spike / HA protein mutant. So the seeding model is actually carrying an incredible load here - 1 Drift mutants must possess a fitness advantage even in a context of sub-clinical infection 2 Everyone on Earth who gets the flu every year must have a chain of contact to the original person who made the new HA mutant 3 There must be some other dynamic that explains the rise in symptomatic illness that doesn't have to do with immune escape / fitness, because the virus already collected those gains during the seeding phase.
Perfect long distance airborne transition restores the link between immune escape / fitness and symptomatic expression, accommodates seeding in drift years and doesn't require it in new subtype/shift years. However, I do think it is weak in terms of plausibility for viability and persistence of the virus in off season.
Thus, in essence, the virus behaves both like it is a species (as it does in avian flu, where there is more genetic diversity) in that it seems to rely on widespread subclinical infection and a single organism (no genetic diversity) in that an immune escape phenotype displaces all other genomes every year. SARS-CoV-2 appears to behave the same way, but this may be an artifact of continued lab release.
Thank you for the concise explanation.
And yes, I'm suggesting the seeding model. Humans seed in one area and from there it rapidly spreads inter-community. Hence in the 1782 likely the seeding happened earlier than Johnson thinks it did. It was already spreading, similar just like in 2020 when we noticed the outbreaks, we later learned there was already community spread for weeks.
I'd imagine with modern sequencing we would more easily proof prove or disprove these models, as long distance spread would have different patterns of micro-mutations than the seeding model.
(Although in modern times, with cars etc you'd also get more cross spread, and you'd be more sensitive in quality of contact tracing.)
My main concern is long distance travel would indeed break with most ideas about limited viability based on physics. Hence I'm not ready to depart from there. But then again, most of this field is just a few decades old, so I'm sure we humans have lot to learn.
The issue that every person must have a link to the 'new HA mutant 3' is curious, indeed. But doesn't covid kind of proves it? Summer 2019 there was nothing. A year later it was everywhere. Omicron repeated that. So, the seed model worked in the initial spread, even if there is a role in long distance later on!
The more pressing problem IMHO is why e.g. Omiron could push out Delta despite plenty of non-immune hosts remaining. Similar like the total die out of old flu phenotypes, although that is helped by existing hosts being immune. But I think these are explained by the same two things.
A first level there is the observation that mutations always occur and there *must* be a die-out. No copies are perfect. The more a virus allows drift, to more quicker it inherently will die out replacing itself. This explains why flu strains never remain. For covid this is less of a factor as mutations seems to be less effective in immune escape due to the fact covid targets a receptor and not a generic aminoacid and hence has less flexibility in effective mutations.
So the 2nd and remaining question is why do some types prevail and others not? I personally suspect this is just an artifact of math/randomness. Most infected people don't infect anybody outside their household and hence being a dead end. Just a few infect multiple. So average R-values are misleading as most have R=0 but a few have large R's. Hence randomness causes most sub-strains to inherently die out. The ones with either an evolutionary benefit or a biochemical likelihood to exist, will prevail.
See it as a game of musical chair dance game. Every turn a few seats are taken away. But then every 3rd turn all seats are placed back due to natual immunity fading. The new seats will be taken by clones of the remaining players. Just mathematically the one that has the largest presence after the 2nd turn, will have more chance to take the chairs that are put back. That is how Deta died out, and how some flu drift directions die out.
But I admit none of all this is a perfect explanation, so there is certainly room for alternatives or compliments. It may not be one or the other, but some interacting factors too.
RE SARS-CoV-2, I regretted comparing the spread dynamics after I posted. SARS-CoV-2 hasn't seemed to defy person-to-person transmission on an interregional level, even if I think it does do so intraregionally.
RE Delta dying out, along with BA.1 pushing back BA.2 when it got a foothold first (as in US, UK, Israel), and then BA.1 dying out, p 172 of "Evolution and Ecology" (my second link in last reply) gives what I think is still the best theory, which that escape mutants raise the antiviral T Cell background response and this crowds out non-escape mutants, leading to the mutant becoming fixed.
RE receptors, the residues that directly bind sialic acid are usually described as highly conserved. In fact I forget whether there are multiple motifs across subtypes or types at all, other than host-specific galactose linkage. Also, this conserved loop is non-immunogenic (https://www.nature.com/articles/289373a0). But the sites around are highly immunogenic and labile, though again seem to be conserved when there is no immune pressure (as in H1N1 swine, and in avian HAs, p164 of the second link in my previous reply).
But in general your seeding + musical chairs model is probably what I would lean toward if I didn't believe in long distance transmission. Even so, there is a problem with the model in that it suggests the chairs are prohibited from replenishing when there are "more than one" previous players still remaining. There's still a bit of "spooky ex machina" built into the model by this assumption, the model just covers it under a bit of cloth.
I should go ahead and posit my current working theory, which is that we frequently have persistent last-season viral replication still going on well into the next season, which is both tolerated in terms of not being totally cleared but suppressed in terms of not being symptomatic. A novel HA/NA mutant does in fact spread at the rate of apparent transmission, implying long distance transmission. These genes, despite being carried in what would otherwise be "dead" flu virions, land in cells that currently contain slowly-replicating residual virus, like a song transmitting into radios that are already turned on, waiting to play it. For this reason the HA and NA genes behave like a single organism while other other six flu "internal" genes show genetic diversity in humans - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC110138/ - Just what determines the fitness of new HA/NA mutants does still seem to be immune escape, at least in my current view.
This theory isn't strictly meant to explain observed fast transmission during "pandemics" - which frequently result in replacement of the internal genes as well, or might usually occur when there are no more residual infections to piggy-back off. But it does offer a spin-off model where new avian (re-)crossovers seed the population of the Earth under similar tolerance / suppression, until once again a mutant HA / NA gene combo disseminates at observed transmission speeds, implying long distance airborne transmission. This "first" mutant HA / NA might be more related to host tropism than immune escape.
Still I am not so wedded to this model as to think it is required for long-distance transmission in a nonsegmented genome, as with SARS-CoV-2.
Oh deer! Is this study something the CDC will fawn over? Or will the buck stop here?
......I'll see myself out now.
I did come up with one (1) deer-related pun title for this review, but I forgot it when I temporarily shelved the post. It isn't the same pressure to perform when I only use puns for sub-titles now, haha.
So...on a serious note....what is the long term ramification here?
If deer "may serve as a reservoir for variant SARS-CoV-2 strains that no longer circulate in the human population," then how likely is it that said SARS-CoV-2 strains will spillback into the human population on a large scale (e.g. like the delta wave), especially since they once circulated in humans?
And, in light of the Ig4 tolerance study, if the B cells of the 2X+ vaccinated are programmed to make Ig4 antibodies when the immune system is challenged by SARS-CoV-2, then wouldn't such a spillover be "like paper and fire" (to quote JC Mellencamp)?
In other words, if 60-70% of the population have their immune systems primed to tolerate SARS-CoV-2 rather than fight it, it seems to me that these deer reservoirs could be the source for a real pandemic ala GVB (albeit a different mechanism than his model).
Is this a ticking time bomb?
I would suggest that what is probably transpiring is the end of Silence of the Lambs crane shot. Wild-animal-crossover-Delta, or even BA.1, melting into a sea of oblivious tourists, with no yet-apparent mortality impact.
IgG4 tolerance may prolong viral clearance even while antibodies still nullify viremia and severe outcomes. However, pulmonary vasculature might get a lot more gooey from retro-crossover-Delta vs. the non-TMPRSS2-requiring Omicron strains, in which case severe outcomes would not be as well-prevented. Result: Ominous crane shot, check back next sequel...
Of course all that assumes deer to human back transmission.
Other than Kid-petting and other zoos or so I don't see how, other than incidental. Unlike with large chicken and pork factories where human workers daily have an opportunity to cross-infect like woth flu, this doesn't look like a common route. And the occasional back jump would hit a wall of large human immunity.
The only thing that would be worrying IMHO is, if inside deer we would get unique mutations, and these mutations would not hurt its capabilities to infect humans back and would cause higher lethality and escape immunity from older strains. But that are a lot of if's. And that would require deer-to-deer transmission, to cultivate these mutations and I'm not convinced on that too.
In that sense the Mink farms were more worrisome. This deer-reservoir seems more a puzzle than a worry to me at this point.
Also it might have been "Deer Fludence," which doesn't even work for a SARS-CoV-2 study.
::shaking my head:: Thank goodness you didn't go with that. 😄
ba dum tiss 🥁
(Hello fellow Buckeye!)
Go Bucks! (no pun intended this time lol)
👍 😀
Hi Brian,
From Caserta et al "The pathways of human-to-deer transmission of SARS-CoV-2, however, are not yet understood." Lines 105,106
Over at the Ethical Skeptic, a plausible pathway is suggested:
https://theethicalskeptic.com/2021/11/15/chinas-ccp-concealed-sars-cov-2-presence-in-china-as-far-back-as-march-2018/
Ah, true, he does mention it - related to fecal transmission if I remember correctly. There's a lot of good insights in that thesis, but I'm not sure it's more compelling than Gamma crossing over in spring via airborne route and then being maintained in deer.
It's likely that many wildlife biologist or conservationists have tagged animals in the wild that they monitor and so maybe at some point they decided to check on Bambi to evaluate for things such as deer ticks and other pathogens and happened to find out that they had COVID.
"I bagged another zombie one, Ross - can you, you know, 'gussy it up a bit'?"
You were reminding me of a terrible CGI deer that made its rounds around the internet. Sure enough, it was from The Walking Dead:
https://www.youtube.com/watch?v=KPxTVJWkbX4
Good point - I didn't think to look into that. Wildlife disease surveillance / control always strikes me as very "op-y" to begin with. Like, is this expensive compared to airborne rabies vaccine scattering, etc... The money's definitely out there, but it is weird not to list a grant
Tingling noted. Perhaps it was all accomplished with after-hours work, hence the long time to get it to preprint. That's doubtful but kind of endearing to imagine.
Don't see any obvious clues in the supplemental material metadata. Pdf has Martins' name / email as the author (as opposed to Joey@CIA.gov etc).
On twitter, all I see so far is "Happy to share our latest preprint. Great collaboration with Dr. Schuler, Cornell Wildlife lab and NYSDEC!" from Diel https://mobile.twitter.com/DiegoDiel1/status/1565829400049901568
Ah, I see. The previous entry in the deer series similarly lacks a grant - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010197#ack - Whereas a different recent publication from "The Diel Lab" (https://diellab.net/publications/) lists loads of funding sources, including start-up funds from Cornell https://www.nature.com/articles/s41586-022-04661-w#Ack1 So it could just be that Diel and co have too much money to even figure out who to "bill" for their deer pet project.