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The Causes of Long Covid(science.org)
96 points by maxall4 4 hours ago | 33 comments
timr 8 minutes ago | parent | next [-]

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 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.

setopt 5 minutes ago | parent [-]

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?

lend000 2 hours ago | parent | prev | next [-]

I had a long process with this that mostly manifested as exercise intolerance and general inflammation/discomfort, and sleep struggles. I made no progress for 2 years, lost most of my muscle (I had been very active before) and started thinking "is this how it's going to be forever?". After not finding anything promising from traditional medicine or supplements, I finally made some dramatic life changes. I'm fully past it now (with persistent lifestyle changes), but I really had to rethink my relationship with food.

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.

nurettin an hour ago | parent | next [-]

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.

mpreda an hour ago | parent | next [-]

Water fast is when the only intake is water (plus electrolites and vitamines). Basically "eat nothing".

empressplay an hour ago | parent | prev [-]

no you only consume water

stringfood 2 hours ago | parent | prev [-]

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.

sebasv_ 2 hours ago | parent | prev | next [-]

I am really grateful to see this still gets attention.

amelius 29 minutes ago | parent | prev | next [-]

Why are women far more likely to have long covid?

Earw0rm 20 minutes ago | parent [-]

Perhaps because it involves immune system dysregulation.

deminature 2 hours ago | parent | prev | next [-]

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.

smj-edison an hour ago | parent | prev | next [-]

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.

_3u10 an hour ago | parent | next [-]

You used to be able to order a paper version but here it is.

https://web.expasy.org/pathways/

smj-edison an hour ago | parent [-]

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.

_3u10 an hour ago | parent | prev [-]

Also, many people have cured chronic illnesses such as Crohn’s disease by moving to countries with low levels of those diseases.

smj-edison an hour ago | parent [-]

Source? Never heard of this before.

MrBuddyCasino 2 hours ago | parent | prev | next [-]

"Long Covid" isn't unique, there were similar reported malaises after major epidemics throughout history:

https://www.cell.com/cms/10.1016/j.it.2025.10.010/asset/0b5a...

This is the corresponding article about this phenomenon, "The lingering shadow of epidemics: post-acute sequelae across history":

https://www.cell.com/trends/immunology/fulltext/S1471-4906(2...

While this seems to validate those syndromes as having real underlying physical causes, I do have to mention that you can treat this (and fibromyalgia) surprisingly well with psychiatric medication, implying there is at least a substantial fake element to it.

Put differently: some people probably get the real thing, but if you can successfully treat a large percentage with SSRIs (which you can, see https://www.nature.com/articles/s41598-023-45072-9), that means they got it by social contagion, like the dancing plague.

Earw0rm 13 minutes ago | parent | next [-]

Not necessarily fake. Mind/body homeostasis is WAY more complicated than that.

To use a computing analogy, which doesn't map perfectly onto the body, if consciousness awareness is userland, you can have things go wrong which are localised in ring 0 - brain drugs will be to some degree effective on those, that doesn't mean it's fake or made up.

In reality there are fuzzy boundaries and feedback loops everywhere. SSRIs treating this isn't any more mysterious than NSAID painkillers being somewhat effective for acute depression.

It's probably a whole set of feedback processes that get screwed up, hence the panoply of symptoms, inserting a hard stop into one part of the loop can be enough to kick the system back into a better functioning state.

kennywinker 2 hours ago | parent | prev | next [-]

That you can see improvements in people with long covid by giving them SSRIs isn’t clear evidence it’s partly fake or a “social contagion”. Whatever improvements recorded are just as easily explained by the fact that being sick for months is depressing and alienating and a bunch of people think you’re faking it.

On top of that, the SSRI article you linked suggests a biochemical mechanism by which SSRIs might be acting (i.e. not by making something “fake” go away, by actually treating the cause of something real)

MrBuddyCasino 41 minutes ago | parent [-]

Why then do SSRIs also work on fibromyalgia, Morgellons, Chronic Lime and Chronic Fatigue?

Aurornis 17 minutes ago | parent [-]

Morgellons isn’t a real disease. It’s a mental health condition.

SSRIs do not “work on” those other conditions, but depression is highly comorbid with serious chronic illnesses. SSRIs improving some symptoms is to be expected when depression symptoms overlap with the condition.

deminature 2 hours ago | parent | prev | next [-]

>implying there is at least a substantial fake element to it.

The article actually argues against that reading: IgG transferred from patients into mice reproduced the symptoms. Mice don't have a nervous disposition. That points to a physical mechanism.

nerevarthelame 2 hours ago | parent | prev | next [-]

Every study that suggests viability of SSRIs to treat or prevent Long COVID presents plausible mechanisms for why they might have that effect. And none of them are "the patients are probably just sad and faking it."

FooBarWidget 16 minutes ago | parent [-]

Symptoms caused by sadness are not necessarily fake.

Earw0rm 11 minutes ago | parent [-]

"Cause" is necessarily a slippery concept in a dynamic system governed by feedback loops so complex that we only understand maybe 20%.

cyberax 4 minutes ago | parent | prev | next [-]

> that means they got it by social contagion

There are studies that show significant immunomodulatory effects of SSRIs.

tehjoker 2 hours ago | parent | prev [-]

FTA:

"

Importantly, IgG fractions from the blood of these individuals cross-reacted with several types of mouse tissue in vitro, and transfer of this IgG to living mice reproduced symptoms such as pain, fatigue, coordination problems, temperature sensitivity and more. These effects were not seen with IGg transfer from unaffected patients. It hardly needs pointing out that you cannot transfer a nervous disposition or a persistent bad attitude by transfusing antibody fractions. Long Covid is a real a disease as lupus, MS, Hashimoto’s, or Type I diabetes, all of which are driven by production of antibodies to a person’s own tissues."

uwagar 39 minutes ago | parent | prev | next [-]

anything else but the vaccine can be a cause.

hhh 5 minutes ago | parent [-]

how would you explain people without the vaccine getting long covid?

prh8 3 hours ago | parent | prev | next [-]

Sadly, no mention of Mast Cell Activation Syndrome, or even mast cells at all

Matticus_Rex 2 hours ago | parent | next [-]

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.

sebasv_ 2 hours ago | parent | prev [-]

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.

FionaZhu an hour ago | parent | prev [-]

Maybe intermittent fasting could help treat it.