The Causes of Long Covid(science.org)
science.org
The Causes of Long Covid
https://www.science.org/content/blog-post/causes-long-covid
131 comments
Having gone through this too, I also had to accept that a lot (not all!) of it was in my head and made worse by it. When I convinced myself that “this will pass” and “this slow steady plan will get me out of this eventually” was when I finally saw regular progress (progress, not immediate relief).
I'm glad that this was the case for you, but presenting it as an universal truth is extremely cruel and harmful to people for whom it is not, and you should be really careful with phrasing. Statements like these is why people's symptoms are not being taken seriously.
It's amazing how powerful the mind is and it's also sad that the default setting is to use that power against oneself
There is absolutely truth to this.
How do you prepare/deal through a water fast? What kind of supplemens would be needed for the water?
Can I read up on this anywhere? I'd welcome a suggestion over surfing the many many pages I found through a simple search. A book or paper reccomendation to read up on would be nice as well
Can I read up on this anywhere? I'd welcome a suggestion over surfing the many many pages I found through a simple search. A book or paper reccomendation to read up on would be nice as well
Honestly AI overviews are a pretty good guide, ask about a 3-5 day water fast. I was nervous going into my first one, but now I don't worry about it. The main thing is to drink a lot of water and have 1-3 LMNT electrolyte packs (unflavored, no sugar) per day, depending on how much you're sweating/exercising (which you absolutely can do, especially the first 2 days).
You can expect to feel colder as your body doesn't conserve as much heat, and after ~2 days more lethargic physically, but your mental energy may actually be higher. I don't sleep as well when fasting, so 3 nights is about my limit. That being said, you feel rested on less sleep, because your body is probably producing a lot less waste.
You can expect to feel colder as your body doesn't conserve as much heat, and after ~2 days more lethargic physically, but your mental energy may actually be higher. I don't sleep as well when fasting, so 3 nights is about my limit. That being said, you feel rested on less sleep, because your body is probably producing a lot less waste.
A non-inflammatory rocket shock diet can certainly aid in symptoms of long covid in many users, often people megadose on antioxidants to dilate their recovery window and not regress. Glad to hear you are feeling better and I totally agree that movement and diet are key in recovering from inflammatory disease.
How do you manage zone 5 cardio 4x a week without PEM?
I thought up to 3x a week and never consecutive days is the maximum.
I thought up to 3x a week and never consecutive days is the maximum.
Zone 5 is usually 1-2 minutes out of a longer 30 minute cardio session for me, I do it as a final sprint. I am not talking about repeated hill sprints where you would get 10+ minutes of zone 5 cardio in a session, which I agree would not be something a normal person should do 4x/week.
From my own experience, it seems like hitting that Zone 5 briefly is a good nervous system reset (overrides any dysfunctional breathing and heart rate effects from long covid); it's less about training the heart, although that's an excellent side effect.
From my own experience, it seems like hitting that Zone 5 briefly is a good nervous system reset (overrides any dysfunctional breathing and heart rate effects from long covid); it's less about training the heart, although that's an excellent side effect.
> hitting that Zone 5 briefly is a good nervous system reset
I ended up doing this inadvertently earlier this week due to some medication side effects (yay akathisia!) making me want to go outside and just seriously run fast, including up the nasty hill nearby. Which I could, so I did. I'm amazed at how much it seems to have helped, for how simple it was. (Another one from the past, though for different situations: alternating hot and cold showers.)
I ended up doing this inadvertently earlier this week due to some medication side effects (yay akathisia!) making me want to go outside and just seriously run fast, including up the nasty hill nearby. Which I could, so I did. I'm amazed at how much it seems to have helped, for how simple it was. (Another one from the past, though for different situations: alternating hot and cold showers.)
What do you mean by water fasting? Do you avoid drinking water directly, or do you avoid all food? For example salads are basically sacks of water.
Water fast is when the only intake is water (plus electrolites and vitamines). Basically "eat nothing".
> Basically "eat nothing".
Thanks for this, reading "water fast" and "3 days" gave me a shot of adrenaline. The "water" prefix is just confusing, the word for abstaining from food is just "fast" for those interested.
If this is engagement bait, then well played..
Thanks for this, reading "water fast" and "3 days" gave me a shot of adrenaline. The "water" prefix is just confusing, the word for abstaining from food is just "fast" for those interested.
If this is engagement bait, then well played..
It is a specific type of fasting. Saying only "fasting" can mean a lot of things, saying "water fast" means you only drink water.
https://en.wikipedia.org/wiki/Fasting
https://en.wikipedia.org/wiki/Fasting
Fair enough, thanks for sharing
Water fasting is used to differentiate from dry fasting, where you don't even drink water.
Is this even a thing? Never assumed you'd ever want to dehydrate like this on purpose. Just why?
dry fasts aren't always what they appear. if you have significant glycogen stores in your body as you begin your fast you wont be dehydrated for the first day or two as water is freed. what usually happens is someone who starts glycogen endowed discovers that they aren't thirsty when they start fasting and tout it as dry fasting.
Ok glycogen store was the only possibilty I has in mind. Thanks:)
Religious Jews have a couple of 25 hour complete fasts per year.
Look up how Muslims fast during Ramadan.
What you thought of (not even drinking water) is called a dry fast. It is a thing, but for obvious reasons is much more intense and shorter in duration.
[deleted]
no you only consume water
I'm happy you got better - but isn't healthy diet, moderate regular exercise and good sleep hygiene staples of traditional medicine?
Thanks. Unfortunately, not really, especially where diet is concerned. For example, I saw significant improvement after removing wheat, white rice, red meat, and dairy entirely, which is not something your typical US doctor would suggest. The first doctor I saw wanted to put me on antidepressants.
I also think exercise recommendations are generally too low, especially with respect to high intensity cardio.
I also think exercise recommendations are generally too low, especially with respect to high intensity cardio.
Before you can investigate the causes of an illness, you have to define it. Otherwise, you’re chasing an ever-shifting cloud of ambiguous symptoms, any of which could have different causes. The article opens with this admission, so I’m not stating anything new here.
The problem with “Long Covid” as it exists today is that there’s no such definition. Literally anyone who had Covid once and feels bad today (and quite a few people who never had a confirmed case at all) includes their set of symptoms in the communal diagnosis. Thus, if you dig into these studies, you always find that the syndrome is a wide-ranging and variable constellation of symptoms, making it impossible for a study to have any systematic legitimacy. Moreover, the results of any particular study are more strongly influenced by the inclusion criterion (if there even is one) than by any other factor.
It’s perfectly possible to evaluate treatments in this situation, and would be a better use of resources - pick symptoms, make an inclusion criteria, and run a randomized trial of existing drugs or therapies. But this is likely to fail, and it’s much, much easier to write papers with unprovable theories and retrospective analysis.
The problem with “Long Covid” as it exists today is that there’s no such definition. Literally anyone who had Covid once and feels bad today (and quite a few people who never had a confirmed case at all) includes their set of symptoms in the communal diagnosis. Thus, if you dig into these studies, you always find that the syndrome is a wide-ranging and variable constellation of symptoms, making it impossible for a study to have any systematic legitimacy. Moreover, the results of any particular study are more strongly influenced by the inclusion criterion (if there even is one) than by any other factor.
It’s perfectly possible to evaluate treatments in this situation, and would be a better use of resources - pick symptoms, make an inclusion criteria, and run a randomized trial of existing drugs or therapies. But this is likely to fail, and it’s much, much easier to write papers with unprovable theories and retrospective analysis.
Sometimes the symptoms are so ambiguous that it is hard to nail anything down. It’s the same thing with Lymes disease, which is definitely a real thing, but there aren’t good, reliable tests for it. It takes a long time to manifest and the symptoms vary wildly from person to person.
> It’s the same thing with Lymes disease, which is definitely a real thing, but there aren’t good, reliable tests for it
There are actually good, reliable tests for it. However Lyme disease (not Lymes disease) became an alternative medicine explanation for everything vague and many people became obsessed with thinking they had it based on vague symptoms like fatigue. When they couldn’t get positive test results to confirm their belief, the Lyme disease online communities established the idea that the tests cannot detect their version of the disease. It’s a belief that allows anyone to diagnose with Lyme disease in a completely unprovable way.
> and the symptoms vary wildly from person to person.
This belief is an unfortunate result of the online Lyme communities encouraging everyone with any unexplained symptoms to believe it’s caused by Lyme disease that can’t be detected. When the disease becomes redefined as being untestable and causing wildly different symptoms in everyone, it becomes impossible to say that anyone doesn’t have it. If you have any vague symptoms like feeling tired, a Lyme disease community will encourage you do believe that it’s caused by an undetectable case of Lyme disease.
There is a lot of strong evidence that these patients do not have Lyme disease, but they’re always good at coming up with another reason why they have it but it can’t be detected in them specifically
There are actually good, reliable tests for it. However Lyme disease (not Lymes disease) became an alternative medicine explanation for everything vague and many people became obsessed with thinking they had it based on vague symptoms like fatigue. When they couldn’t get positive test results to confirm their belief, the Lyme disease online communities established the idea that the tests cannot detect their version of the disease. It’s a belief that allows anyone to diagnose with Lyme disease in a completely unprovable way.
> and the symptoms vary wildly from person to person.
This belief is an unfortunate result of the online Lyme communities encouraging everyone with any unexplained symptoms to believe it’s caused by Lyme disease that can’t be detected. When the disease becomes redefined as being untestable and causing wildly different symptoms in everyone, it becomes impossible to say that anyone doesn’t have it. If you have any vague symptoms like feeling tired, a Lyme disease community will encourage you do believe that it’s caused by an undetectable case of Lyme disease.
There is a lot of strong evidence that these patients do not have Lyme disease, but they’re always good at coming up with another reason why they have it but it can’t be detected in them specifically
There are increasingly positive markers - autonomic dysfunction in previously healthy people, measurable small fiber neuropathy, and auto immune dysfunction in largely unmapped parts of the immune system.
Interesting. Someone should (or maybe have?) run a cluster analysis on the symptoms to define more specific subgroups. But I suppose getting access to the required health data at that scale is nontrivial?
It’s not that hard to get a long list of symptoms for long covid. Just watch this thread as it grows, and you’ll easily find dozens. Things like this end up being a lint trap for people who just feel bad for whatever reason (which is all of us, at various points in our lives!) Nobody likes to be told that their symptoms are idiopathic.
Massaging this kind of data (clustering, etc.) is much lower value than finding fixed criteria that define a consistent group of patients who have objectively defined symptoms that cannot be more readily explained by another diagnosis. This is a pre-requisite for any further study. It can be done, but it’s hard, and it tends to lead to criticisms because you end up excluding a large number of people who fervently believe they have the illness, but don’t fit the objective standards.
Just for example: it’s not enough to claim that you have “brain fog”. A more valid endpoint might instead attempt to classify people based on standardized tests of thinking. Even that has problems, of course, but if you can just claim that you are fatigued and unable to think clearly, there’s a huge problem of confounding (i.e. maybe your symptoms are caused by something else), let alone the unverified nature of the original claim.
Massaging this kind of data (clustering, etc.) is much lower value than finding fixed criteria that define a consistent group of patients who have objectively defined symptoms that cannot be more readily explained by another diagnosis. This is a pre-requisite for any further study. It can be done, but it’s hard, and it tends to lead to criticisms because you end up excluding a large number of people who fervently believe they have the illness, but don’t fit the objective standards.
Just for example: it’s not enough to claim that you have “brain fog”. A more valid endpoint might instead attempt to classify people based on standardized tests of thinking. Even that has problems, of course, but if you can just claim that you are fatigued and unable to think clearly, there’s a huge problem of confounding (i.e. maybe your symptoms are caused by something else), let alone the unverified nature of the original claim.
Leading research into Long Covid is already doing this. You’re seeing neural and auto immune clusters gathering around certain immune dysfunction and previously rare diagnosis like Small Fiber Neuropathy. Autonomic dysfunction is being measured in young and healthy people also, and that has its own set of objective testing.
Everything you are saying is happening. But because the suspicion seems more and more that it’s an auto immune condition of some sort, and that we are only catching the downstream effects as some of the immune dysfunction isn’t mapped yet, we are seeing the clusters that you say emerge - overwhelming numbers of symptoms, relatively incoherent connection.
But autonomic dysfunction, small fiber neuropathic and detectable auto immune dysfunction are all known and increasingly mapped positive markers for the condition. Have you read the latest studies ?
Everything you are saying is happening. But because the suspicion seems more and more that it’s an auto immune condition of some sort, and that we are only catching the downstream effects as some of the immune dysfunction isn’t mapped yet, we are seeing the clusters that you say emerge - overwhelming numbers of symptoms, relatively incoherent connection.
But autonomic dysfunction, small fiber neuropathic and detectable auto immune dysfunction are all known and increasingly mapped positive markers for the condition. Have you read the latest studies ?
> You’re seeing neural and auto immune clusters gathering around certain immune dysfunction and previously rare diagnosis like Small Fiber Neuropathy.
Everything I've personally seen in this space is exactly what I described: they start with a set of people who claim to have the illness, then go on a statistical fishing expedition to look for "signs of immune disfunction" (or whatever, but you're right that these researchers tend to focus on immune-related metrics), then use whatever signals they happen to find to create a class. This is not the same thing as what I'm talking about, and it isn't valid.
I'm not going to claim comprehensive knowledge of the space, but the papers I've read that make it into the high-profile journals are of this sort.
The papers cited by this Lowe article are better than most at least in the sense that they have control groups and are doing experiments. But let's be clear -- the first one is claiming to see "long covid" pain symptoms in mice who are injected with whole human IgG (a notoriously messy and subjective approach) [1], and the other is exactly the kind of fishing expedition I'm describing, where they indiscriminately look for "targets" of said antibodies [2]. The former is at least doing an experiment that I suppose could lead to some kind of claim of cause, but the latter (despite the exaggerated title) provides no evidence that the correlations they're seeing are meaningful in any disease process.
I guarantee that using the high-dimensional screening that the latter paper in particular is doing, I can take 1000 random people, split them into two arbitrary classes ("fooists" and "non-fooists"), and find some "statistically significant" difference in immune marker profile between them. That is the fundamental problem with the approach.
When I say that you have to start from an objective measurement of symptoms, it means literally that -- not starting from an assay result that is unlinked to any symptom.
[1] https://www.sciencedirect.com/science/article/pii/S266637912...
[2] https://www.sciencedirect.com/science/article/abs/pii/S00928...
Aside: this lab is becoming infamous for this kind of statistical fishing expedition. It makes me cry for the state of science.
Everything I've personally seen in this space is exactly what I described: they start with a set of people who claim to have the illness, then go on a statistical fishing expedition to look for "signs of immune disfunction" (or whatever, but you're right that these researchers tend to focus on immune-related metrics), then use whatever signals they happen to find to create a class. This is not the same thing as what I'm talking about, and it isn't valid.
I'm not going to claim comprehensive knowledge of the space, but the papers I've read that make it into the high-profile journals are of this sort.
The papers cited by this Lowe article are better than most at least in the sense that they have control groups and are doing experiments. But let's be clear -- the first one is claiming to see "long covid" pain symptoms in mice who are injected with whole human IgG (a notoriously messy and subjective approach) [1], and the other is exactly the kind of fishing expedition I'm describing, where they indiscriminately look for "targets" of said antibodies [2]. The former is at least doing an experiment that I suppose could lead to some kind of claim of cause, but the latter (despite the exaggerated title) provides no evidence that the correlations they're seeing are meaningful in any disease process.
I guarantee that using the high-dimensional screening that the latter paper in particular is doing, I can take 1000 random people, split them into two arbitrary classes ("fooists" and "non-fooists"), and find some "statistically significant" difference in immune marker profile between them. That is the fundamental problem with the approach.
When I say that you have to start from an objective measurement of symptoms, it means literally that -- not starting from an assay result that is unlinked to any symptom.
[1] https://www.sciencedirect.com/science/article/pii/S266637912...
[2] https://www.sciencedirect.com/science/article/abs/pii/S00928...
Aside: this lab is becoming infamous for this kind of statistical fishing expedition. It makes me cry for the state of science.
Then you should fund it. The entire field is to my understanding absolutely starved of science funding.
There are two fairly strong clusters of findings that are objective, repeatable, and consistent. And that is the autonomic testing in long COVID patients is coherent in its dysfunction, and so is the Small Fiber Neuropathy testing that is now consistently showing abnormalities.
Lets go step by step.
Small Fiber Neuropathy. Nerve fiber density is a count with age/sex-normed reference ranges. In previously healthy post-COVID patients with no diabetes and no risk factor, then the test shows whether the nerves are there or they aren't.
https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1284&c...
https://www.medrxiv.org/content/10.1101/2025.03.04.25323101v...
https://www.neurology.org/doi/pdf/10.1212/NXI.00000000002002...
https://pmc.ncbi.nlm.nih.gov/articles/PMC12847426/pdf/fnhum-...
We have brain structure changes showing in the UK Biobank studies https://pmc.ncbi.nlm.nih.gov/articles/PMC9046077/
Associations with complement dysregulation https://www.cell.com/med/fulltext/S2666-6340(24)00041-2
Muscular abnormalities in long COVID patients reporting reduced exercise function https://www.sciencedirect.com/science/article/pii/S104327602...
Potential that persistent infection shows up in Long Covid patients in abnormal rates https://www.massgeneralbrigham.org/en/about/newsroom/press-r...
If your argument is that people are showing up with abnormalities, then diagnosed with Long Covid, then spurious biomarkers are associated to it - you are just wrong. Wrong multiple times. Demonstrably so.
What we are seeing is more likely to be exactly what it looks like - an novel condition being captured by downstream effects of previously unknown or understudied mechanisms.
There are two fairly strong clusters of findings that are objective, repeatable, and consistent. And that is the autonomic testing in long COVID patients is coherent in its dysfunction, and so is the Small Fiber Neuropathy testing that is now consistently showing abnormalities.
Lets go step by step.
Small Fiber Neuropathy. Nerve fiber density is a count with age/sex-normed reference ranges. In previously healthy post-COVID patients with no diabetes and no risk factor, then the test shows whether the nerves are there or they aren't.
https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1284&c...
https://www.medrxiv.org/content/10.1101/2025.03.04.25323101v...
https://www.neurology.org/doi/pdf/10.1212/NXI.00000000002002...
https://pmc.ncbi.nlm.nih.gov/articles/PMC12847426/pdf/fnhum-...
We have brain structure changes showing in the UK Biobank studies https://pmc.ncbi.nlm.nih.gov/articles/PMC9046077/
Associations with complement dysregulation https://www.cell.com/med/fulltext/S2666-6340(24)00041-2
Muscular abnormalities in long COVID patients reporting reduced exercise function https://www.sciencedirect.com/science/article/pii/S104327602...
Potential that persistent infection shows up in Long Covid patients in abnormal rates https://www.massgeneralbrigham.org/en/about/newsroom/press-r...
If your argument is that people are showing up with abnormalities, then diagnosed with Long Covid, then spurious biomarkers are associated to it - you are just wrong. Wrong multiple times. Demonstrably so.
What we are seeing is more likely to be exactly what it looks like - an novel condition being captured by downstream effects of previously unknown or understudied mechanisms.
All of those are examples of exactly what I told you about: they take a group of people claiming to be sick, and go hunting for signals to claim as “significant”.
The MRI studies are particularly egregious examples of this. Just because you see a difference on an MRI does not mean that the difference is due to the thing you’re blaming. In fact, it almost never is.
> If your argument is that people are showing up with abnormalities, then diagnosed with Long Covid, then spurious biomarkers are associated to it - you are just wrong. Wrong multiple times. Demonstrably so.
I am? I have now followed every link. Literally every paper you posted is following this exact pattern. I don't know how you could possibly conclude otherwise, unless you just didn't read past the titles.
They each take a (typically small) cohort of people who self-identify as "long covid sufferers", they subject them to random combinations of tests, and report only what they find to be significant. It's literally the XKCD comic about jelly beans.
https://xkcd.com/882/
The MRI studies are particularly egregious examples of this. Just because you see a difference on an MRI does not mean that the difference is due to the thing you’re blaming. In fact, it almost never is.
> If your argument is that people are showing up with abnormalities, then diagnosed with Long Covid, then spurious biomarkers are associated to it - you are just wrong. Wrong multiple times. Demonstrably so.
I am? I have now followed every link. Literally every paper you posted is following this exact pattern. I don't know how you could possibly conclude otherwise, unless you just didn't read past the titles.
They each take a (typically small) cohort of people who self-identify as "long covid sufferers", they subject them to random combinations of tests, and report only what they find to be significant. It's literally the XKCD comic about jelly beans.
https://xkcd.com/882/
You are just ignoring the evidence, being unscientific, and unless you work for a top medical lab somewhere, plain arrogant.
The UK Biobank study scanned participants before and after infection with matched controls. The difference is measured against their own pre-infection brain. That is the opposite of what you're describing.
The UK Biobank study scanned participants before and after infection with matched controls. The difference is measured against their own pre-infection brain. That is the opposite of what you're describing.
> You are just ignoring the evidence, being unscientific, and unless you work for a top medical lab somewhere, plain arrogant.
If you don't know how to interpret evidence, then I suppose it would sound like I am being overly critical. I didn't bother to pick on just one, but since you chose it [1]...
> The UK Biobank study scanned participants before and after infection with matched controls. The difference is measured against their own pre-infection brain. That is the opposite of what you're describing.
It is not. The longitudinal nature of the study is a distraction from the fundamental issues with the approach.
They did a longitudinal case-control study, one group of which had positive covid tests in the past, and the other one did not at the time of the second scan (2021). That's the entire evidence base that this study is built upon -- it has nothing to do with "long Covid", and it's only barely plausible that the control group is actually a control for the factors of interest.
Next, they took two scans for all participants - one from before the pandemic, and one made after (again, in 2021). They made over 6000 different images, and then cherry-picked the ones with differences for further analysis (~70). Ultimately only 6 of these fishing expeditions survived family-wise error correction:
> The main case-versus-control analysis between the 401 SARS-CoV-2 cases and 384 controls (Model 1) on 297 olfactory-related cerebral IDPs yielded 68 significant results after FDR correction for multiple comparisons, including 6 that survived FWE correction
So first off, no statistical correction can compensate for this fundamental bias. You cannot start with thousands of different samples - even if they're taken from the same people at different time points - and winnow that down to a handful by filtering on the outcome of interest, Applying a multiple-sample correction will not fix it. It's not even clear that there is such a correction that is valid for the underlying distribution of the data involved.
But setting that aside, the differences observed, even between longitudinal samples, do not have to be due to Covid! Even if they're not random (which we cannot grant; see previous paragraph) they could be due to everyone being locked inside during 2020. They could be due to factors completely unexamined by the study, like, say, increases in drinking or drug use, or lack of exercise. Or any of a million other things. We don't know. The authors don't know. They're just not intellectually honest enough to admit that they don't know.
I could go on, and point out more flaws (e.g. the "significant" results mostly disappear when you exclude hospitalized patients, yet oddly, the difference between "hostipitalized" and "control" cohorts is not itself significant, indicating inadequate statistics), but this post is already too long.
I'm sorry that you think this is arrogant, but this is how we actually read papers.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9046077
If you don't know how to interpret evidence, then I suppose it would sound like I am being overly critical. I didn't bother to pick on just one, but since you chose it [1]...
> The UK Biobank study scanned participants before and after infection with matched controls. The difference is measured against their own pre-infection brain. That is the opposite of what you're describing.
It is not. The longitudinal nature of the study is a distraction from the fundamental issues with the approach.
They did a longitudinal case-control study, one group of which had positive covid tests in the past, and the other one did not at the time of the second scan (2021). That's the entire evidence base that this study is built upon -- it has nothing to do with "long Covid", and it's only barely plausible that the control group is actually a control for the factors of interest.
Next, they took two scans for all participants - one from before the pandemic, and one made after (again, in 2021). They made over 6000 different images, and then cherry-picked the ones with differences for further analysis (~70). Ultimately only 6 of these fishing expeditions survived family-wise error correction:
> The main case-versus-control analysis between the 401 SARS-CoV-2 cases and 384 controls (Model 1) on 297 olfactory-related cerebral IDPs yielded 68 significant results after FDR correction for multiple comparisons, including 6 that survived FWE correction
So first off, no statistical correction can compensate for this fundamental bias. You cannot start with thousands of different samples - even if they're taken from the same people at different time points - and winnow that down to a handful by filtering on the outcome of interest, Applying a multiple-sample correction will not fix it. It's not even clear that there is such a correction that is valid for the underlying distribution of the data involved.
But setting that aside, the differences observed, even between longitudinal samples, do not have to be due to Covid! Even if they're not random (which we cannot grant; see previous paragraph) they could be due to everyone being locked inside during 2020. They could be due to factors completely unexamined by the study, like, say, increases in drinking or drug use, or lack of exercise. Or any of a million other things. We don't know. The authors don't know. They're just not intellectually honest enough to admit that they don't know.
I could go on, and point out more flaws (e.g. the "significant" results mostly disappear when you exclude hospitalized patients, yet oddly, the difference between "hostipitalized" and "control" cohorts is not itself significant, indicating inadequate statistics), but this post is already too long.
I'm sorry that you think this is arrogant, but this is how we actually read papers.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9046077
This seems to me like a performance at this point and not serious analysis.
It’s true I conflated this with long covid. It’s not a long covid study.
I am tired and done with this. You made several errors in this comment.
Your biggest error is the lockdown one.
This makes no sense whatsoever - the controls also lived through lockdown. If this is the rigorous analysis you’re bringing to the studies you read, I’m not surprised none of them pass the muster.
“No correction can fix it” is wrong because the olfactory IDPs were pre-specified. “Could be lockdown” is wrong because controls lived through the same lockdown. “Results disappear excluding hospitalized” is wrong because the paper says they persisted.
The statistical weaknesses you describe are in the papers own limitations section. You just read them back as limitations that can’t be surpassed while evidence based researchers in the field disclose them as meaningful but not exclusionary.
Unless you want to continue with debunking every other strong paper I’ve posted with similar limited and likely to be demonstrably wrong takedowns, then I can’t help you. You have unfalsifiable priors, are constantly ignoring evidence and seem to believe you know better than the top researchers in the field - people who are saving lives - because you catch some statistical limitations and imply that they debunk the entire thing, instead of accepting them as limits of incomplete research into a real condition that’s crippling millions of people.
It’s true I conflated this with long covid. It’s not a long covid study.
I am tired and done with this. You made several errors in this comment.
Your biggest error is the lockdown one.
This makes no sense whatsoever - the controls also lived through lockdown. If this is the rigorous analysis you’re bringing to the studies you read, I’m not surprised none of them pass the muster.
“No correction can fix it” is wrong because the olfactory IDPs were pre-specified. “Could be lockdown” is wrong because controls lived through the same lockdown. “Results disappear excluding hospitalized” is wrong because the paper says they persisted.
The statistical weaknesses you describe are in the papers own limitations section. You just read them back as limitations that can’t be surpassed while evidence based researchers in the field disclose them as meaningful but not exclusionary.
Unless you want to continue with debunking every other strong paper I’ve posted with similar limited and likely to be demonstrably wrong takedowns, then I can’t help you. You have unfalsifiable priors, are constantly ignoring evidence and seem to believe you know better than the top researchers in the field - people who are saving lives - because you catch some statistical limitations and imply that they debunk the entire thing, instead of accepting them as limits of incomplete research into a real condition that’s crippling millions of people.
> the controls also lived through lockdown. If this is the rigorous analysis you’re bringing to the studies you read, I’m not surprised none of them pass the muster.
You've missed the point. I'm not suggesting that the other factor or factors has to be "lockdown". I'm just giving examples that illustrate the idea: even if you assume that the differences between the control and the experimental group are non-random and significant, you still cannot attribute the longitudinal difference to the one factor alone. If you don't like my theory, it's easy to find another, if you're even a little bit imaginative.
> “Results disappear excluding hospitalized” is wrong because the paper says they persisted.
No. They lose all but one. The final "significant" result is teetering on the edge of insignificance. See table 4 [1]. Models 2-4.
> the statistical weaknesses you describe are in the papers own limitations section.
Yes, because they're real. It's great that they wrote them in the paper, but they're fatal flaws.
"We openly disclosed the reason our study is nonsense!" is not the damning indictment you're suggesting that it is.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9046077/table/Tab4/
You've missed the point. I'm not suggesting that the other factor or factors has to be "lockdown". I'm just giving examples that illustrate the idea: even if you assume that the differences between the control and the experimental group are non-random and significant, you still cannot attribute the longitudinal difference to the one factor alone. If you don't like my theory, it's easy to find another, if you're even a little bit imaginative.
> “Results disappear excluding hospitalized” is wrong because the paper says they persisted.
No. They lose all but one. The final "significant" result is teetering on the edge of insignificance. See table 4 [1]. Models 2-4.
> the statistical weaknesses you describe are in the papers own limitations section.
Yes, because they're real. It's great that they wrote them in the paper, but they're fatal flaws.
"We openly disclosed the reason our study is nonsense!" is not the damning indictment you're suggesting that it is.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9046077/table/Tab4/
Yes of course.
It’s lockdown and now no lockdown. Could be anything. All observational studies are wrong. The stated limitations are fatal flaws. You heard it here first in HN. All medical research is fatally flawed, says user “timr”.
Good luck with that.
It’s lockdown and now no lockdown. Could be anything. All observational studies are wrong. The stated limitations are fatal flaws. You heard it here first in HN. All medical research is fatally flawed, says user “timr”.
Good luck with that.
I’m not even sure you understand how evidence based medicine works.
Afaik evidence based medicine ranks mechanistic analysis near the bottom of the hierarchy — below controlled trials and systematic observation. I believe that ordering was a deliberate choice.
You seem obsessed with something that modern medical research often doesn’t focus on - by design. We still don’t know how lithium works 50 years past its introduction. We don’t know how the conditions that it treats - psychosis or bipolar - work either. Yet lithium is used all over the world- because the effects data and reports show that it works. Your mechanistic obsession isn’t just wrong - it’s directionally incorrect as far as a lot of medical research goes.
Afaik evidence based medicine ranks mechanistic analysis near the bottom of the hierarchy — below controlled trials and systematic observation. I believe that ordering was a deliberate choice.
You seem obsessed with something that modern medical research often doesn’t focus on - by design. We still don’t know how lithium works 50 years past its introduction. We don’t know how the conditions that it treats - psychosis or bipolar - work either. Yet lithium is used all over the world- because the effects data and reports show that it works. Your mechanistic obsession isn’t just wrong - it’s directionally incorrect as far as a lot of medical research goes.
MCAS is pretty well defined and is associated with it.
I know someone's case who got it 3 times. The first 2 times full recover in no time. The third one took couple of months and now feels tired all the time, lost all sense of taste and smell, swollen tongue, body pain of sitting still due to the compression of muscles.
This person told me it was sure it was related to COVID because there was nothing before or after it and that was the only thing that happened.
Kinda sucks to thing that everytime it might be a chance for that or worse
This person told me it was sure it was related to COVID because there was nothing before or after it and that was the only thing that happened.
Kinda sucks to thing that everytime it might be a chance for that or worse
I had covid 7 or 8 times lol. Basically 2-3 times a year from Jan 2022 until spring of 2025. Luckily there have been seemingly no long-term effects for me, and it's been over a year since I last tested positive.
Maybe tell this person to see an autonomic dysfunction expert.
Not sure if needed. It depends much on your exposure. If you have someone on your family it is a factor of risk.
Which just makes things insane considering that they exploit it get couple hundred bucks more per insurance.
It has been cheaper to not work for the healthcare system lately. Also because people are a**oles to nurses and the rest of the staff.
It has been cheaper to not work for the healthcare system lately. Also because people are a**oles to nurses and the rest of the staff.
I am really grateful to see this still gets attention.
I caught this in the Dec 2023/Jan 2024 Covid wave, in a densely-packed Bay Area tech office. I only returned to near-full mental clarity in Jan 2026 - two years later. It's an insidious illness that needs more visibility. Poorly ventilated offices full of sick colleagues in close proximity are ideal conditions for transmitting airborne diseases, and it's far too easy to develop a debilitating chronic illness this way. There should be minimum clean-air standards for open offices to protect workers.
Why are women far more likely to have long covid?
The leading hypothesis is the same one that explains why women get more autoimmune disease generally. Women mount stronger immune responses than men - protective in acute infection (men had worse acute COVID outcomes), but it comes at a cost: women are the large majority of lupus, MS, Hashimoto's and RA cases. If long covid is substantially autoimmune/inflammatory, as the autoantibody findings in the OP article suggest, the group already primed for autoimmunity is the one you'd expect to be hit hardest. Proposed drivers: immune-regulating genes on the X chromosome (e.g. TLR7) and estrogen being immunostimulatory where testosterone is suppressive.
Are they though?
and from that study:
The results follow a 2024 study led by Dr Mulu Woldegiorgis that surveyed 11,000 people from Western Australia three months after they contracted COVID-19. Almost one-in-five (18.2 per cent) had developed long COVID. The researchers then monitored the same group of people six months after their initial infection.
“We wanted to get a sense of the trajectory for people with long COVID. After six months, the average number of symptoms remained stable, indicating little improvement,” she said.
and from that study:
In multivariable analyses, pre-existing health conditions at the time of initial SARS-CoV-2 infection and reporting fatigue, shortness of breath, and cough 3 months post-infection were independent predictors of persistent long COVID.
Age, sex, and number of COVID vaccinations were not significantly associated with persistent long COVID.
I've heard things hypothesized to be either differences in hormone levels, or the one that's more fascinating to me is it could be because an issue came up with suppressing the second X chromezone.
Some speculation is the pill. Some kind of unmapped interaction.
Perhaps because it involves immune system dysregulation.
Covid almost killed me. I distinctly remember feeling near death when the hospital attempted a last-ditch effort with a transfusion. I don’t remember all of the details, but I know that someone, somewhere, saved my life. And I’ve done fuck all with that gift — it’s been almost five years.
Personally, the only long Covid symptom I know of is that I have a coughing fit after every meal (and sometimes during). Some foods seem to lead to worse fits, but anything other than liquid will make me cough to some degree. Sometimes, it’s to the point that I see stars and nearly pass out.
All in all, I got off easy with Covid. It could have been worse.
Personally, the only long Covid symptom I know of is that I have a coughing fit after every meal (and sometimes during). Some foods seem to lead to worse fits, but anything other than liquid will make me cough to some degree. Sometimes, it’s to the point that I see stars and nearly pass out.
All in all, I got off easy with Covid. It could have been worse.
> coughing fit after every meal (and sometimes during).
This might be stomach acid aspirating into your lungs, from GERD or similar caused/exacerbated by Covid, and that may have negative consequences for your health apart from the coughing.
This might be stomach acid aspirating into your lungs, from GERD or similar caused/exacerbated by Covid, and that may have negative consequences for your health apart from the coughing.
Maybe a bit of a strange take, but after having dealt with chronic illness personally and talked with a lot of others with chronic illness, I don't think classifying chronic illness by symptoms will help with curing, and in fact I don't think categorizing works at all for chronic illness. We've been trying to classify chronic illnesses for so long, and yet in most cases no pattern emerges.
This has led me to conclude that perhaps in most cases chronic illness is an emergent behavior from a complex system, namely our body. Now tbh this is kind of a cheap take, because it's not that hard to conclude. But gosh darn it, we're programmers and we deal with complex systems all the time! What I want to see is a complete quantitative mapping of human metabolism, so that we can see all the in-between steps, not just the surface levels. That way curing chronic illness is more about comparing metabolite levels against known pathways and seeing what's regulated incorrectly. There's just not enough introspective capability currently.
My vision is some day a person who's been chronically ill can walk into a clinic, take a blood test, and with mass spectrometry get the level of the around 1800 different intermediate metabolites. That gets mapped to a known good metabolic graph, and it's optimized to find what in-between step is off kilter. They're then prescribed a drug that resets the bad state, and it 6 weeks they're back to normal.
I also doubt that AI will substantially help either. It still doesn't bring any more introspection capability, and if we can't figure out why someone is sick, I have little faith that a predictive AI can figure it out either.
This has led me to conclude that perhaps in most cases chronic illness is an emergent behavior from a complex system, namely our body. Now tbh this is kind of a cheap take, because it's not that hard to conclude. But gosh darn it, we're programmers and we deal with complex systems all the time! What I want to see is a complete quantitative mapping of human metabolism, so that we can see all the in-between steps, not just the surface levels. That way curing chronic illness is more about comparing metabolite levels against known pathways and seeing what's regulated incorrectly. There's just not enough introspective capability currently.
My vision is some day a person who's been chronically ill can walk into a clinic, take a blood test, and with mass spectrometry get the level of the around 1800 different intermediate metabolites. That gets mapped to a known good metabolic graph, and it's optimized to find what in-between step is off kilter. They're then prescribed a drug that resets the bad state, and it 6 weeks they're back to normal.
I also doubt that AI will substantially help either. It still doesn't bring any more introspection capability, and if we can't figure out why someone is sick, I have little faith that a predictive AI can figure it out either.
You used to be able to order a paper version but here it is.
https://web.expasy.org/pathways/
https://web.expasy.org/pathways/
Thanks for the link! I looked over it, but I'm not seeing quantitative levels of reactions. That's been my biggest issue with current pathway databases. It's great to know what's connected to what, but very quickly it becomes everything connected to everything. And unfortunately everything doesn't reduce the problem space.
That would be difficult - a metabolic map is a diagram showing the known reactions. At any point in time, only a subset of these will be active. Like a road map - at midnight, only some roads will have traffic.
I think what you are looking for is more like a model of the metabolome, showing the flow through the network under certain conditions (steady-state, growth, cell stress, etc). Not sure if there is a readily available database of such models, or how easy it would be just to run them and get meaningful results.
I think what you are looking for is more like a model of the metabolome, showing the flow through the network under certain conditions (steady-state, growth, cell stress, etc). Not sure if there is a readily available database of such models, or how easy it would be just to run them and get meaningful results.
Yeah, I think that's closer to what I'm looking for. I'm actually looking into scaling up chemical simulation, so hopefully simulating it is feasible in the near future!
people are doing this for ME/CFS patients, and trying stuff, and ... it's not easy at all. But the signs at least are pointing toward something coherent.
Yes, it's many variants from a disease, but still, like cancer we can tackle them one by one.
https://www.youtube.com/watch?v=ldg2AdVnlOs
https://www.nature.com/articles/s41598-026-46965-1
If it would be easy already data from 2016 would have "solved" it, right?
https://www.pnas.org/doi/10.1073/pnas.1607571113
Yes, it's many variants from a disease, but still, like cancer we can tackle them one by one.
https://www.youtube.com/watch?v=ldg2AdVnlOs
https://www.nature.com/articles/s41598-026-46965-1
If it would be easy already data from 2016 would have "solved" it, right?
https://www.pnas.org/doi/10.1073/pnas.1607571113
Welcome to alternative health :))) there are many functional doctors, and others who perform this kind of stuff.
For example Organic Acids in Urine Test gives you some 70-80 metabolic markers, which some folks interpret. There's no large scale RCTs or studies on this, so it's a bit dubious. But I did one and the practitioner correctly read the leaves to suggest some things that were missing and which helped me (glutathione and B1).
For example Organic Acids in Urine Test gives you some 70-80 metabolic markers, which some folks interpret. There's no large scale RCTs or studies on this, so it's a bit dubious. But I did one and the practitioner correctly read the leaves to suggest some things that were missing and which helped me (glutathione and B1).
> For example Organic Acids in Urine Test gives you some 70-80 metabolic markers, which some folks interpret.
The alternative medicine people use these tests because when you measure 80 different things you are almost guaranteed that some of them will come up high or low.
What they don’t explain is that many of them are expected to fluctuate and will show up with very different values on different days or depending on what you’ve eaten or when you’re taking the test.
They like it because they can tell you that you are too low in this thing and therefore you need to take this other supplement, every time someone takes the test.
For someone who isn’t getting answers from regular doctors it feels like a miracle that someone finally tested them, diagnosed them, and gave them something to take with a simple explanation of why it explains everything. This is the perfect recipe for placebo responses, which are common.
The forums are interesting to read because most people who do these and take the supplements will be very positive at first, but then over time they go back and take another test and find the results are completely different because it’s so random.
Organic acids tests are mostly only useful in the context of diagnosing specific genetic deficiencies which produce severe changes in the test results. The minor ups and downs that the alternative medicine people try to use are not diagnostic, especially with only a single test.
The alternative medicine people use these tests because when you measure 80 different things you are almost guaranteed that some of them will come up high or low.
What they don’t explain is that many of them are expected to fluctuate and will show up with very different values on different days or depending on what you’ve eaten or when you’re taking the test.
They like it because they can tell you that you are too low in this thing and therefore you need to take this other supplement, every time someone takes the test.
For someone who isn’t getting answers from regular doctors it feels like a miracle that someone finally tested them, diagnosed them, and gave them something to take with a simple explanation of why it explains everything. This is the perfect recipe for placebo responses, which are common.
The forums are interesting to read because most people who do these and take the supplements will be very positive at first, but then over time they go back and take another test and find the results are completely different because it’s so random.
Organic acids tests are mostly only useful in the context of diagnosing specific genetic deficiencies which produce severe changes in the test results. The minor ups and downs that the alternative medicine people try to use are not diagnostic, especially with only a single test.
This has been my experience. After not getting answers for a long time from conventional doctors, I went to a naturopath out of desperation. I was diagnosed with "mold toxicity", and took a bunch of supplements to boost all the low levels I had (B12 and cortisol). I also took flax seeds to help with "detox". All the stuff helped a bit, but only a bit. It was still just symptom fighting.
Now to be fair, there are people whose lives have been changed by these treatments, because in some cases someone just happens to be low in some essential micronutrient, and seeing a naturopath solves that when a traditional doctor didn't do a broad assay. But it still doesn't help people like me where whatever is happening can't be described by surface level blood tests and treatments. Naturopaths talk about "wholistic health", but if it's so wholistic, why don't they consider intermediate reactions? So it's become a life goal of mine to build a quantitative metabolic reaction database. I'm currently a applied math major with a chemistry minor, so in a couple years I hope to be able to make some headway on this.
Now to be fair, there are people whose lives have been changed by these treatments, because in some cases someone just happens to be low in some essential micronutrient, and seeing a naturopath solves that when a traditional doctor didn't do a broad assay. But it still doesn't help people like me where whatever is happening can't be described by surface level blood tests and treatments. Naturopaths talk about "wholistic health", but if it's so wholistic, why don't they consider intermediate reactions? So it's become a life goal of mine to build a quantitative metabolic reaction database. I'm currently a applied math major with a chemistry minor, so in a couple years I hope to be able to make some headway on this.
Also, many people have cured chronic illnesses such as Crohn’s disease by moving to countries with low levels of those diseases.
Source? Never heard of this before.
I don't find it far fetched. If there are environmental causes then moving would help.
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uwagar(2)
camcaine(2)
throw9393r93(1)
This author and the article is utterly and chronically useless and cringe. It offers no insight. If you want something that's more useful:
Long COVID may be fueled by inflammation and tiny clots (2026)
https://www.sciencedaily.com/releases/2026/01/260107225532.h...
Long COVID may be fueled by inflammation and tiny clots (2026)
https://www.sciencedaily.com/releases/2026/01/260107225532.h...
Maybe intermittent fasting could help treat it.
Sadly, no mention of Mast Cell Activation Syndrome, or even mast cells at all
It'd have been interesting for them to discuss it, but from what I understand it looks like MCAS is probably an entirely separate thing (that can also be triggered by COVID), but because of the overlap in symptoms, many people who assumed they have long COVID actually had MCAS. And even after teasing those two out, there may be more conditions in the long COVID bucket.
And of course people can have both.
And of course people can have both.
This is a blog on the root cause. MCAS would be an intermediate mechanism in making you feel sick, but something must have triggered the MCAS. Thats the autoimmune response.
MCAS is the underlying condition, which is then triggered by a Covid infection. This results in an escalation of baseline symptoms, which is what Long Covid is
Ended up doing a paleo diet, avoiding stressors (some of which are not obvious like just being on your phone scrolling, bad posture/circulation/sitting for too long), improving sleep hygiene, and ramping up consistent cardio exercise, with an emphasis on getting up to 4x/week zone 5 cardio without triggering intolerance.
Since then I've discovered a lot of other things that are great for overall health, like HRV-reset breathing and long-duration water fasts (around 3 days is optimal for me). I imagine those would have been very helpful if I had tried them earlier. A water fast is a complete metabolic and inflammatory reset of the body, and it's not as hard as you might think.
Hopefully most affected folks have recovered and are living normal lives by now, but if not, there are things you can do! It seems like the more challenging those things are, the more efficacious.