ICU delirium is an long accepted phenomenon sometimes lasting for months after discharge. As an RN I can testify to the atrocity of locking someone into a room and depriving them of the company of anyone who might care about them (except of course random 'space suited' staff who were overwhelmed with just the donning of equipment before even going into the room). These people often didn't even see a smile, so the previous post wondering about how being locked down might much more negatively impact the sick...even those who were home and sick is worth a study or two. I was 69 when I had covid in oct'20. I completely lost my smell for one week while I also experienced severe headache, body pain, exhaustion and general misery. When I recovered, my sense of smell came back quickly. My 48yo daughter had very mild symptoms but her sense of smell is still impaired. I want you to know that I enjoy your stack. It is like being back in college, though in a class way too advanced for me. Even though you slammed a stack I really like, (I read about twenty) I really appreciate different points of view so that my opinions aren't so deeply entrenched that I can't learn. I would like you to address the similarities and differences between antibiotic resistance and vaccine resistance at some point if you have time. I find it odd that I never see this issue discussed by the scientists who insist that the unvaccinated are responsible for the mutations in this virus. Would they also say that those who never use antibiotics are responsible for mutations in bacteria and fungus? I am pretty sure that it is overuse of antibiotics as in earaches, colds and of course the pervasive use in agriculture that is driving the antibiotic/antifungal resistance that kills over one million people a year. I would like to know if I am mistaken. Thanks for a really great read.
Thank you for the thoughtful remarks and kind comments!
The trauma of ICU itself is a really important confounder in so many studies of the virus, especially the literature for cardiac outcomes. It is absolutely a hazard when looking at neuro outcomes as well, which is why I think this study is stronger for using such a loose definition for cases and having so few hospitalized (as well as for showing the same effects with the hospitalized removed).
I'm slowly working my way toward that. It's complicated because, as you say, it's an obvious question so why isn't anyone asking it? It's a giant negative space in the research - "why do we keep adding to the number of viruses which we put unnatural evolutionary pressures on?" but also, "why haven't we been punished for doing so yet with polio, etc"? And the reason for this negative space is obvious - "vaccines are safe and effective" is all anyone is allowed to publish.
It's also a complicated issue with bacteria, because some antibiotic resistance is driven by genes that live in phages (viruses of bacteria - so, it's actually more reversible since the "genome" of the bacteria isn't actually changing, just the distribution of phages), and because we know that you can be exposed to pathogenic strains and still be fine, as they can't get a foothold in a well-established microbiome.
So I'm not sure where to take things, but it's definitely a subject I intend to attack.
I believe I covered this study, albeit in preprint form, a few months ago. It's interesting to what extent our CNS has been targeted. I'm looking up papers on Long COVID to write about but the CNS seems to have been a target of prior infections as well. It's fascinating to wonder how much of our brain chemistry has been affected by prior viruses. I think this area has been severely overlooked, especially because neurological changes may mostly manifest as changes in mental health which tend to be brushed off by many in the medical community.
I have some very out-there theories on the subject of viruses and the nervous system. I made a first draft of them in my Immune Equilibrium essay - https://unglossed.substack.com/p/burned-all-my-notebooks - but even viewing the matter conservatively, it seems that our nervous system is yet another biological niche that is "colonized" by viruses from early age, and this may have impacts on personality, and immunization against chicken pox may be causing some type of accidental and by-definition unnatural mass personality alteration for the kids growing up after the 90s!
Considering that we nonchalantly refer to shingles as the reemergence of herpes zoster without fully describing how the virus hides away within our CNS until the immune system is too weak to keep it in check and I wonder if there's a lot more we tend to gloss over. This is also making me wonder if myelination of neurons does not just increase signaling but may provide a protective barrier against pathogens. Sigh, even more things to consider.
And it may be the case that "onboarding" (my term) of lysogenic viruses in certain tissues promotes transcription "barrier strengthening" genes. We know that CMV promotes expression of viperin in immune cells, and viperin blocks other would-be immune-invaders like HIV. So does chicken pox defend against later post-viral neuropathies? Does measles defend against later immunodeficiency (or have a synergistic relationship of suppressing the immune system for a few years in childhood to promote "onboarding" of other viruses)? Just as with bacteria it's presumptuous for medicine to assume that the space occupied by childhood viruses is meant to be left empty.
I think we tend to forget that germ warfare is not host vs microbes, but microbes vs microbes. One of the worst sins in teaching biology is the way that people gloss over the fact that penicillin's discovery was because some scientist was too sloppy and left a petri dish open without understanding that mold, requiring its own nutrients, will kill off other microbes that would otherwise occupy the same space.
One of my organic chemistry professors did his PhD thesis on this compound made by bacteria to fight off other bacteria and that they essentially battled each other in a tit-for-tat scenario to continuously modify the compound that they deployed.
I think the teaching of science has been a bit disingenuous to think that viruses and bacteria may not want other pathogens to take up their own space and may actually work against that happening, possibly benefitting the host passively.
Conversely, this is why the regional differences in the "consensus microbiome" may alone explain varying degree of susceptibility to a certain virus. But there's likely multiple things going on.
Btw, I noticed your comment on the I1221T mutation - that would be Threonine, not Tyrosine. So it's certainly a surprising mutation in that it's not destructive to the TM domain!
Yes, you are right. The whole abbreviation for amino acids are horrible. I should have remembered that Tyrosine is one of the "phonetically abbreviated" amino acids. Science just does not know how to name things properly!
Did they factor in the lockdowns? Particularly with alzheimers, etc, having contact with people you know and a regular schedule of activities helps maintain cognitive function.
Certainly all that in Australia was switched off via lockdowns and people died because of it.
What if susceptibility to infection is just one symptom of an underlying subtle health issue, and susceptibility to brain changes another? I don't see how this study show causality.
That falls under the first bullet. The study design does the most that you can really ask for as far as putting participants on an even playing field, and if the effect is in fact a marker of underlying susceptibility it still means that testing positive is a risk factor (and still means that individuals are not averages).
However, it’s really just plausible that (untreated) infection in the elderly causes brain changes. If the virus is near the brain there will be inflammation, if it is in the brain then it will destroy neurons. This is why memory / humoral immunity has a role.
Had it just after Christmas. Lost smell on 2nd or third day. That was weird. Had a mild fever a few days that sort of came and went and the usual aches and pains associated with a cold. By 3rd day was back to about 80% then to 100% over the next 3-4 days. Day 4 was out working in the yard. Took nothing except some aspirin two nights for aches. I've had much worse colds and flu. I am 67 YO. Smell has totally returned.
I'm a fan of pointless fights, but I've noticed you sometimes work way too hard arguing pointless positions. I'd like to express my gratitude to you for not making me endure the next installment of your "Want To Believe" serial. I suppose next you'll be arguing whether air exists. Or curiosity.
I wonder if changes in brain tissue after lung infection could be related to oxygen deprivation. The brain is notoriously sensitive to non optimal conditions. Alcohol is said to kill brain cells, which might explain some of their bizarre arguments we hear sometimes. I wonder if the spike protein antigens, or even the mrna capsules can even penetrate the blood brain barrier. The brain does a fairly good job of keeping out most molecules it doesn't like, preferring to manufacture what it needs. Observations of brain changes are probably valid, but conjecture about causes needs some work.
I'm still glad the authors here went out on a limb to do the conjecture bit, since brain regional networks are so esoteric it's not like I would have thought up their theory on my own. But yes, it's reaching. Again, we have no idea of the baseline - it's not like we find out about the virus-induced changes to our nerves that don't result in symptoms, and our understanding of how common these types of events + eventual full recovery are in childhood is probably incomplete, imo.
My hunch is that outright ischemia would fall in the "not subclinical" / "not disguised as brain fog" category, however. But it's a complicated question. But for my own two days of brain fog post infection in January, I'm not worried about the "how." Whatever the mechanism, I don't notice any lingering effects. Maybe the virus ate up every brain cell in my head; doesn't seem to be making a difference so why worry. As for alcohol, it can have a few cells (if any are still in there).
The LNPs can probably get into pituitary / pineal gland since there's more capillary fenestration there, and those cells might be accounting for neurological effects post-vaccination.
A TV is set up to play Escape to the Country. The TV is moved around in the view of the Brit, to see if the Brit tries to follow the TV with their gaze.
I’ve had phantom smells since December 2020 when I had Covid. My only symptoms were a fever of 102 and diarrhea. I did not get tested then, but my daughter had tested positive the day before I got sick. I was sick for a day or two, but woke up o e morning to a terrible smell. It was constant for the longest and at times, I was sure it was me. Now it comes and goes. I’m used to it, but have recently realized that it’s probably neurological damage. I’ll be 65 this month, so I guess I’m in the category you’re referring to.
I'm behind on the recent research that has come out regarding the mechanism of the smell thing (I think I have two different papers on it open in tabs somewhere), so I can't really guess if that would suggest a neurological element. But it's interesting that I've seen other anecdotes of "sensory hallucinations," and I even had a weird night of waking up and hearing phantom sounds for several hours last summer! It followed a scratchy throat; maybe it was Delta. But here, again, this is probably not a new thing, other viruses probably have always played these mind tricks too.
The main argument around anosmia has been whether the olfactory nerves themselves are being targeted or if peripheral cells important for olfactory signaling are what's to blame. I think the most recent evidence I have seen suggest that the latter may be occurring, although the former would at least make for a compelling argument for neuroinvasion. It's the supposition I used to argue about how the virus is gaining entryway into the CNS considering it's the first route into the body (through the nasal passage).
There's a few studies suggesting oral > lower respiratory > nasal, at least for the "Wuhan" (pre-Omicron) strains. Another area where my research is disorganized, but the recent challenge study shows throat before nose - https://www.researchsquare.com/article/rs-1121993/v1 and this early breakthrough one finds mouth before nose (squares are oral swabs in Fig 1; ignoring the newly-vaccinated as they were possibly already mid-infection) https://www.medrxiv.org/content/10.1101/2021.08.30.21262701v1
Interesting. Reading the abstract it doesn't differentiate between nose or throat entryway as they were provided it intranasally. I would assume that the throat's reduced ability to filter pathogens and the possibly lower mucus production may contribute to the virus taking host there before the nose. It's a reason why "mouth breathers" are actually one of the worst things for people healthwise since they won't have the filtering abilities the nose would (among other health issues).
*That* I did not know. But the whole upper airway is a fascinating area on account of being so evolutionarily compromised! Perhaps why the littlest behavioral changes can result in failure.
Not many people realize how dangerous it actually is to breathe through your mouth instead of your nose. It's related to a large number of diseases. I think people just think of it within the context of sleep apnea and not just every day regular breathing.
Well, we do have to keep in mind evolution did not make us perfect, it made us adequate!
ICU delirium is an long accepted phenomenon sometimes lasting for months after discharge. As an RN I can testify to the atrocity of locking someone into a room and depriving them of the company of anyone who might care about them (except of course random 'space suited' staff who were overwhelmed with just the donning of equipment before even going into the room). These people often didn't even see a smile, so the previous post wondering about how being locked down might much more negatively impact the sick...even those who were home and sick is worth a study or two. I was 69 when I had covid in oct'20. I completely lost my smell for one week while I also experienced severe headache, body pain, exhaustion and general misery. When I recovered, my sense of smell came back quickly. My 48yo daughter had very mild symptoms but her sense of smell is still impaired. I want you to know that I enjoy your stack. It is like being back in college, though in a class way too advanced for me. Even though you slammed a stack I really like, (I read about twenty) I really appreciate different points of view so that my opinions aren't so deeply entrenched that I can't learn. I would like you to address the similarities and differences between antibiotic resistance and vaccine resistance at some point if you have time. I find it odd that I never see this issue discussed by the scientists who insist that the unvaccinated are responsible for the mutations in this virus. Would they also say that those who never use antibiotics are responsible for mutations in bacteria and fungus? I am pretty sure that it is overuse of antibiotics as in earaches, colds and of course the pervasive use in agriculture that is driving the antibiotic/antifungal resistance that kills over one million people a year. I would like to know if I am mistaken. Thanks for a really great read.
Thank you for the thoughtful remarks and kind comments!
The trauma of ICU itself is a really important confounder in so many studies of the virus, especially the literature for cardiac outcomes. It is absolutely a hazard when looking at neuro outcomes as well, which is why I think this study is stronger for using such a loose definition for cases and having so few hospitalized (as well as for showing the same effects with the hospitalized removed).
I'm slowly working my way toward that. It's complicated because, as you say, it's an obvious question so why isn't anyone asking it? It's a giant negative space in the research - "why do we keep adding to the number of viruses which we put unnatural evolutionary pressures on?" but also, "why haven't we been punished for doing so yet with polio, etc"? And the reason for this negative space is obvious - "vaccines are safe and effective" is all anyone is allowed to publish.
It's also a complicated issue with bacteria, because some antibiotic resistance is driven by genes that live in phages (viruses of bacteria - so, it's actually more reversible since the "genome" of the bacteria isn't actually changing, just the distribution of phages), and because we know that you can be exposed to pathogenic strains and still be fine, as they can't get a foothold in a well-established microbiome.
So I'm not sure where to take things, but it's definitely a subject I intend to attack.
I believe I covered this study, albeit in preprint form, a few months ago. It's interesting to what extent our CNS has been targeted. I'm looking up papers on Long COVID to write about but the CNS seems to have been a target of prior infections as well. It's fascinating to wonder how much of our brain chemistry has been affected by prior viruses. I think this area has been severely overlooked, especially because neurological changes may mostly manifest as changes in mental health which tend to be brushed off by many in the medical community.
I have some very out-there theories on the subject of viruses and the nervous system. I made a first draft of them in my Immune Equilibrium essay - https://unglossed.substack.com/p/burned-all-my-notebooks - but even viewing the matter conservatively, it seems that our nervous system is yet another biological niche that is "colonized" by viruses from early age, and this may have impacts on personality, and immunization against chicken pox may be causing some type of accidental and by-definition unnatural mass personality alteration for the kids growing up after the 90s!
Considering that we nonchalantly refer to shingles as the reemergence of herpes zoster without fully describing how the virus hides away within our CNS until the immune system is too weak to keep it in check and I wonder if there's a lot more we tend to gloss over. This is also making me wonder if myelination of neurons does not just increase signaling but may provide a protective barrier against pathogens. Sigh, even more things to consider.
And it may be the case that "onboarding" (my term) of lysogenic viruses in certain tissues promotes transcription "barrier strengthening" genes. We know that CMV promotes expression of viperin in immune cells, and viperin blocks other would-be immune-invaders like HIV. So does chicken pox defend against later post-viral neuropathies? Does measles defend against later immunodeficiency (or have a synergistic relationship of suppressing the immune system for a few years in childhood to promote "onboarding" of other viruses)? Just as with bacteria it's presumptuous for medicine to assume that the space occupied by childhood viruses is meant to be left empty.
I think we tend to forget that germ warfare is not host vs microbes, but microbes vs microbes. One of the worst sins in teaching biology is the way that people gloss over the fact that penicillin's discovery was because some scientist was too sloppy and left a petri dish open without understanding that mold, requiring its own nutrients, will kill off other microbes that would otherwise occupy the same space.
One of my organic chemistry professors did his PhD thesis on this compound made by bacteria to fight off other bacteria and that they essentially battled each other in a tit-for-tat scenario to continuously modify the compound that they deployed.
I think the teaching of science has been a bit disingenuous to think that viruses and bacteria may not want other pathogens to take up their own space and may actually work against that happening, possibly benefitting the host passively.
Conversely, this is why the regional differences in the "consensus microbiome" may alone explain varying degree of susceptibility to a certain virus. But there's likely multiple things going on.
Btw, I noticed your comment on the I1221T mutation - that would be Threonine, not Tyrosine. So it's certainly a surprising mutation in that it's not destructive to the TM domain!
Yes, you are right. The whole abbreviation for amino acids are horrible. I should have remembered that Tyrosine is one of the "phonetically abbreviated" amino acids. Science just does not know how to name things properly!
Did they factor in the lockdowns? Particularly with alzheimers, etc, having contact with people you know and a regular schedule of activities helps maintain cognitive function.
Certainly all that in Australia was switched off via lockdowns and people died because of it.
Yes. Controls were also locked down, and the pattern of changes didn’t correspond to what was expected for stress. It was a very careful design.
What if susceptibility to infection is just one symptom of an underlying subtle health issue, and susceptibility to brain changes another? I don't see how this study show causality.
That falls under the first bullet. The study design does the most that you can really ask for as far as putting participants on an even playing field, and if the effect is in fact a marker of underlying susceptibility it still means that testing positive is a risk factor (and still means that individuals are not averages).
However, it’s really just plausible that (untreated) infection in the elderly causes brain changes. If the virus is near the brain there will be inflammation, if it is in the brain then it will destroy neurons. This is why memory / humoral immunity has a role.
Had it just after Christmas. Lost smell on 2nd or third day. That was weird. Had a mild fever a few days that sort of came and went and the usual aches and pains associated with a cold. By 3rd day was back to about 80% then to 100% over the next 3-4 days. Day 4 was out working in the yard. Took nothing except some aspirin two nights for aches. I've had much worse colds and flu. I am 67 YO. Smell has totally returned.
Glad to hear it!
I'm a fan of pointless fights, but I've noticed you sometimes work way too hard arguing pointless positions. I'd like to express my gratitude to you for not making me endure the next installment of your "Want To Believe" serial. I suppose next you'll be arguing whether air exists. Or curiosity.
I wonder if changes in brain tissue after lung infection could be related to oxygen deprivation. The brain is notoriously sensitive to non optimal conditions. Alcohol is said to kill brain cells, which might explain some of their bizarre arguments we hear sometimes. I wonder if the spike protein antigens, or even the mrna capsules can even penetrate the blood brain barrier. The brain does a fairly good job of keeping out most molecules it doesn't like, preferring to manufacture what it needs. Observations of brain changes are probably valid, but conjecture about causes needs some work.
I'm still glad the authors here went out on a limb to do the conjecture bit, since brain regional networks are so esoteric it's not like I would have thought up their theory on my own. But yes, it's reaching. Again, we have no idea of the baseline - it's not like we find out about the virus-induced changes to our nerves that don't result in symptoms, and our understanding of how common these types of events + eventual full recovery are in childhood is probably incomplete, imo.
My hunch is that outright ischemia would fall in the "not subclinical" / "not disguised as brain fog" category, however. But it's a complicated question. But for my own two days of brain fog post infection in January, I'm not worried about the "how." Whatever the mechanism, I don't notice any lingering effects. Maybe the virus ate up every brain cell in my head; doesn't seem to be making a difference so why worry. As for alcohol, it can have a few cells (if any are still in there).
The LNPs can probably get into pituitary / pineal gland since there's more capillary fenestration there, and those cells might be accounting for neurological effects post-vaccination.
I’m just wondering how anyone was able to notice declined brain function in a Brit. ;)
A TV is set up to play Escape to the Country. The TV is moved around in the view of the Brit, to see if the Brit tries to follow the TV with their gaze.
Fuckin’ gold. Bahahahaha!
I’ve had phantom smells since December 2020 when I had Covid. My only symptoms were a fever of 102 and diarrhea. I did not get tested then, but my daughter had tested positive the day before I got sick. I was sick for a day or two, but woke up o e morning to a terrible smell. It was constant for the longest and at times, I was sure it was me. Now it comes and goes. I’m used to it, but have recently realized that it’s probably neurological damage. I’ll be 65 this month, so I guess I’m in the category you’re referring to.
I'm behind on the recent research that has come out regarding the mechanism of the smell thing (I think I have two different papers on it open in tabs somewhere), so I can't really guess if that would suggest a neurological element. But it's interesting that I've seen other anecdotes of "sensory hallucinations," and I even had a weird night of waking up and hearing phantom sounds for several hours last summer! It followed a scratchy throat; maybe it was Delta. But here, again, this is probably not a new thing, other viruses probably have always played these mind tricks too.
The main argument around anosmia has been whether the olfactory nerves themselves are being targeted or if peripheral cells important for olfactory signaling are what's to blame. I think the most recent evidence I have seen suggest that the latter may be occurring, although the former would at least make for a compelling argument for neuroinvasion. It's the supposition I used to argue about how the virus is gaining entryway into the CNS considering it's the first route into the body (through the nasal passage).
There's a few studies suggesting oral > lower respiratory > nasal, at least for the "Wuhan" (pre-Omicron) strains. Another area where my research is disorganized, but the recent challenge study shows throat before nose - https://www.researchsquare.com/article/rs-1121993/v1 and this early breakthrough one finds mouth before nose (squares are oral swabs in Fig 1; ignoring the newly-vaccinated as they were possibly already mid-infection) https://www.medrxiv.org/content/10.1101/2021.08.30.21262701v1
Interesting. Reading the abstract it doesn't differentiate between nose or throat entryway as they were provided it intranasally. I would assume that the throat's reduced ability to filter pathogens and the possibly lower mucus production may contribute to the virus taking host there before the nose. It's a reason why "mouth breathers" are actually one of the worst things for people healthwise since they won't have the filtering abilities the nose would (among other health issues).
*That* I did not know. But the whole upper airway is a fascinating area on account of being so evolutionarily compromised! Perhaps why the littlest behavioral changes can result in failure.
Not many people realize how dangerous it actually is to breathe through your mouth instead of your nose. It's related to a large number of diseases. I think people just think of it within the context of sleep apnea and not just every day regular breathing.
Well, we do have to keep in mind evolution did not make us perfect, it made us adequate!
I forgot to mention that my antibodies were checked in July of 2021 and they were positive for Covid.