The Causes of Long Covid

(science.org)

100 points | by maxall4 4 hours ago

16 comments

  • timr 16 minutes ago
    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.

    • setopt 13 minutes ago
      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?
      • timr 1 minute ago
        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.

        Massaging this kind of data (clustering, etc.) is much lower value than finding things that define a consistent group of patients who have objectively defined symptoms. This is a pre-requisite for any further study.

    • dyauspitr 7 minutes ago
      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.
  • lend000 1 hour ago
    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 1 hour ago
      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 1 hour ago
        Water fast is when the only intake is water (plus electrolites and vitamines). Basically "eat nothing".
        • layoric 0 minutes ago
          > 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..

      • empressplay 1 hour ago
        no you only consume water
    • stringfood 1 hour ago
      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.
  • camcaine 6 minutes ago
    After never catching covid but nearly dying from the vaccine, it's (also) vaccine induced.
  • throw9393r93 2 minutes ago
    Everyone knows what is the cause of long "covid", but censhorship is still strong. There are trillion dollars at play, and nobody wants to pay compensations.
  • sebasv_ 2 hours ago
    I am really grateful to see this still gets attention.
  • deminature 2 hours ago
    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.
  • amelius 37 minutes ago
    Why are women far more likely to have long covid?
    • Earw0rm 29 minutes ago
      Perhaps because it involves immune system dysregulation.
  • smj-edison 1 hour ago
    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 1 hour ago
      You used to be able to order a paper version but here it is.

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

      • smj-edison 1 hour ago
        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 1 hour ago
      Also, many people have cured chronic illnesses such as Crohn’s disease by moving to countries with low levels of those diseases.
      • smj-edison 1 hour ago
        Source? Never heard of this before.
  • MrBuddyCasino 2 hours ago
    "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 21 minutes ago
      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.

      • colordrops 5 minutes ago
        Thank you, these overly simplistic first-order-only analysis of extremely complex phenomena drive me nuts.
    • kennywinker 1 hour ago
      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 49 minutes ago
        Why then do SSRIs also work on fibromyalgia, Morgellons, Chronic Lime and Chronic Fatigue?
        • Aurornis 26 minutes ago
          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.

          • MrBuddyCasino 6 minutes ago
            I'm somewhat open to this line of thinking, but it seems in these cases, there is a very fuzzy boundary between the symptoms of depression and "the real illness": brain fog, lack of energy etc.

            I've seen healthy, active and successful people be affected, where the cause of "long covid" seems unlikely to be psychological. But there is no denying that, shall we say "a certain type" of person seems to be overrepresented in these cases, and for them it is very attractive to attach the label "long covid" to something that previously existed.

            I guess that until we have discovered the biological mechanism underlying this phenomenon, it will be hard to cleanly separate these two cases, but from what I've seen I find it likely that this bipartition really exists.

    • deminature 2 hours ago
      >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 1 hour ago
      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 25 minutes ago
        Symptoms caused by sadness are not necessarily fake.
        • Earw0rm 20 minutes ago
          "Cause" is necessarily a slippery concept in a dynamic system governed by feedback loops so complex that we only understand maybe 20%.
    • cyberax 13 minutes ago
      > that means they got it by social contagion

      There are studies that show significant immunomodulatory effects of SSRIs.

    • tehjoker 2 hours ago
      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 48 minutes ago
    [flagged]
    • camcaine 7 minutes ago
      this. the vaccine
    • hhh 14 minutes ago
      how would you explain people without the vaccine getting long covid?
  • aaron695 2 hours ago
    [dead]
  • indiandeodorant 2 hours ago
    [flagged]
  • GenerocUsername 3 hours ago
    [flagged]
  • prh8 3 hours ago
    Sadly, no mention of Mast Cell Activation Syndrome, or even mast cells at all
    • Matticus_Rex 2 hours ago
      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
      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 57 minutes ago
    Maybe intermittent fasting could help treat it.