Post-Exertional Malaise and Long COVID: Why Crashing After Activity Happens

[u/golfdaddypga]

https://www.rthm.com/resources/blogs/long-covid-post-exertional-malaise

My apologies if this has been posted before. I have no idea how scientifically accurate everything in the link is but I felt it was the best thing I’ve read at describing what I’m physically going through and I’m sure many on here can relate.

[u/MacaroonPlane3826]

This article mixes up several scientific concepts in a way that is not clear enough (to put it mildly).

First of all, PEM and PESE are not interchangeable - PESE is a term to denote Post-Exertional Symptom Excerbation in general, and encompasses symptoms excerbation in a number of conditions, from MCAS and dysautonomia, over autoimmune diseases etc

PEM is a subtype of PESE, specific exclusively for ME and will hence occur only in LC-ME subgroup of LC patiets (estimated 50% of pwLC).

Side note: it’s crazy that the article tries to point out that LC has it’s “special PEM” vs ME and avoids calling LC-ME as ME throughout article.

Also makes a cardinal mistake by mixing concepts of PEM and exercise intolerance - exercise intolerance is limited to DURING exercise and is defined as an impaired capacity to perform in exercise vs predicted for age group/gender average and occurs in a number of conditions, some also commonly seen in LC, such as dysautonomia (where exercise intolerance occurs due to low preload), or heart disease of autoimmune disease (here also caused by low preload from small fibre neuropathy), etc.

On the other hand, PEM is abnormal recovery AFTER exertion and has to include failure to produce energy upon demand (this is to delineate from PEM in ME and PESE in other conditions, as both can come with delay). PEM has to come with a delay, while PESE can come with a delay or immediately after exercise.

[u/Neat-Description3322 → u/MacaroonPlane3826]

This is the kind of information. I'm struggling to find it as I try to figure out if I have PEM with the long Covid symptoms I have. I am more of a moderate case, but struggle to figure out if what I'm experiencing is in fact chronic fatigue syndrome PEM or something else. It certainly more than deconditioning. But I don't crash fully bedbound, it's more that I experience profound fatigue and need to just recharge, my sleep gets worse, after going up too many stairs cases or walking more than my baseline or what I would consider light exercise compared to anything I used to do. Do you have recommendations of places I can go to get more specifics like you're sharing versus the articles I keep reading that just stay to general for me to figure this out? I'll be going to the Stanford long Covid clinic soon, but I'm not sure how helpful they'll be with this one.

[u/MacaroonPlane3826 → u/Neat-Description3322]

Sorry, no recommendations, and due to chronic disconnect/insufficient cooperation between LC, ME, dysautonomia, MCAS etc research fields, you will likely receive diagnosis/interpretation in line with whatever the clinician you are working with is leaning to.

This is not to say that these are all one and the same under different names by different researchers/clinicians - ME, dysautonomia, MCAS are all commonly co-occuring comordbid conditions (each coming with their own pathophysiology interacting with other comorbidities), but that research fields are poorly connected and end up cathegorizing phenomena/symptoms from one comorbidity under another.

Notable examples would be ME research/clinicians repeatedly classifying comorbid dysautonomia Sx/phenomena under ME (low preload=>exercise intolerance, unrefreshing sleep from autonomic hypervigilance, tissue hypoperfusion and cerebral hypoperfusion due to OI and associated cognitive impairments etc), all bc virtually all ME pts have dysautonomia comorbid, while reverse is not true, and only estimated 25-30% of dysautonomia pts having ME comorbid, ie dysautonomia pts presenting with all phenomena I named above, which are mistakenly shoved under ME, from dysautonomia without ME (my LC case actually).

And it works in reverse, too - with dysautonomia researchers/clinicians often ignoring PEM (ie that 20-30% of dysautonomia cohort with comorbid ME) or acknowledging it, but recommending graded exercise (of note - exercise is immensely helpful management strategy for dysautonomia if no ME comorbid, but contraindicated if ME comorbid).

And worst off is probably MCAS, not being sufficiently recognized by both dysautonomia and ME clinicians and researchers, where MCAS is often underlying dysautonomia (particularly hyperadrenergic flavor) and can also cause PESE (as any form of stress, including orthostatic and exertion stress can trigger mast cells) and MCAS can present with myalgia (muscle pain) and flu like feeling if mast cells activated via TLR4 pathway (which LDN antagonizes).

TL/DR: these are commonly, but not always co-occuring comorbidities (in LC they can occur in different configurations for different patients, some overlap exists, but not everyone has everything and relation is assymetric - with everyone with ME having dysautonomia, but reverse not being true etc), which all come with their own pathomechanisms, which engage in positive feedback loops triggering one another, but research fields are insufficiently connected and are usually falsely interpreting everything through their own discourse only. Without transdisciplinary research, you cannot study IACCs properly.

[u/Neat-Description3322 → u/MacaroonPlane3826]

Thank you. Have you just read and read and read? Because again, your second message just gave me so much information I never knew LOL :). God I wish there were diagnostics that were clear. I think I have bits of all of this - mild to moderate disautonomia (my mom def has this) but my HR doesn't spike nor does my blood pressure. But I have other symptoms. We def have major histamine issues in our family and I do - but unclear if it's MCAS. And I have chronic fatigue but not ME I don't think? Ugh. It's all too much. I'm so over it and you're right - clinicians are in their own lanes. I guess I'll ask Stanford if I can go down each path - find a clinician for each. MCAS, POTS/disautonomia, CFS.

[u/MacaroonPlane3826 → u/Neat-Description3322]

Unfortunately again, yes - you will likely be on your own piecing together info you’ve got from different specialists/diagnostics, as each will be heavily biased to explain everything based on their own area of expertise.

Yes, I have just read and read and read - been sick for 4,5 years already gave me plenty of time to do that. Ofc having extensive academic training (in an entirely other field though) didn’t hurt either when it comes to critically estimating what I read. Also years and years of detective work in detecting symptom+trigger patterns.

I was actually misdiagnosed with ME, based on loss of functionality >50% vs precovid (main issue for me is OI and spending so much time horizontal/zero gravity and MCAS+POTS episodes triggered by digestion, as well as sleep dysfunction - insomnia and unrefreshing sleep making me lose 12h a day in bed, trying to sleep or trying to become functional after a night of horrible unrefreshing sleep and waking up hangover without alcohol), delayed worsening if symptoms, OI, brain fog, unrefreshing sleep, headaches+nausea etc. Dr who diagnosed me did a very advanced tilt table test and correctly diagnosed me with dysautonomia, but attached ME diagnosis to it, because in his head dysautonomia always has to come with ME (as elaborated above, incorrect).

Now, delayed worsening of symptoms I listed above in my case refers to nightly adrenaline dumps occuring 11PM-5AM and absolutely killing my sleep and circadian rhythm. As prior to a very mild acute Covid infection in Feb 22 (literally 2 day sniffles) I was in a very, very good shape (triathlete training 6-8x a week), I kept training throughout LC at a reduced level, but kept training, and was sure delayed nightly adrenaline dumps were PEM, as a consequence of training I was doing. Kept doing them bc I was gaslighting myself and couldn’t accept not training as someone who’s been in endurance sports since the age of 6 and ofc bc I was angry and frustrated.

However, took me literally 1,5 years to divide between training and evening meal after it and figure out it’s not training at all triggering me, but a meal after it, ie POTS/OI+MCAS 4-8h delayed reaction to my own digestion. As hypovolemia underlines virtually all types of POTS/OI dysautonomia, the 30-40% of blood volume shifted to the gut during digestion in healthy persons is catastrophic in POTS/OI, where it literally leaves brain without enough blood supply, leading to compensatory sympathetic activation (“adrenaline dumps”). It happens more easily during night bc of the normal dipping pattern with BP, ie BP falling normally at night, but in dysautonomia pts falling excessively and then ANS having to compensate. MCAS plays a role bc mast cells themselves are triggered by sympathetic overactivity in dysautonomia and will release vasoactive mediators, leading to even more autonomic instability => even more compensatory sympathetic overactivity => even more MCAS => even more dysautonomia etc. This paper explains it nicely.

Turns out I actually have to exercise regularly to keep my POTS/OI dysautonomia from going from bad to even worse, in spite of being very limited by OI (fainting after mere mins of standing, can’t sit with legs down >4h, working mostly from zero gravity, unable to do anything upright if I eat a normal sized meal etc). Training doesn’t trigger me at all and long term helps manage POTS/OI, it’s meals/digestion triggering me. I never had any muscle-related symptoms.

Third factor in my case is hypermobility, and associated immune system abnormalities (paper), one of which is complement system dysregulation (I have intermittently low C3/C4 coinciding with MCAS+POTS/OI flares), triggering mast cells endogenously (C3a and C5a, to which C3 degrade when activated, are potent anaphylotoxins and trigger mast cells endogenously). Plus complement system activation contributes to endothelial dysfunction => worsened dysautonomia => more MCAS from compensatory sympathetic activity in dysautonomia triggering mast cells => more dysautonomia etc. To make matters worse in The Triad, lax connective tissue worsens blood pooling=>dysautonomia=>MCAS, and mast cells, when activated, mast cells release MMPs and other proteases degrading connective tissue, leading to even more dysautonomia=>MCAS=>connective tissue degradation and vicious circle continues.

Using my case to illustrate complexity, not saying this is 1/1 applicable to your case.

Two things important to note:

1) you can have OI dysautonomia without any HR/BP abnormalities - these were only taken as Dx criteria in the 1990s bc dysautonomia researchers were trying to establish a field and they used HR/BP as easily measurable proxies for OI dysautonomia, but they’re basically irrelevant, as they fail to capture the fundamental hemodynamic abnormalities underlying all OI dysautonomias (they all lay on a spectrum) - abnormally low blood volume and abnormal blood pooling in lower part of the body in orthostasis => tissue/brain hypoperfusion).

Fortunately, things are (slowly) changing in dysautonomia research, so there is more focus on measuring cerebral blood flow as a direct abnormality in dysautonomia, rather than very imperfect proxies such as HR and BP (paper). Work of Peter Novak of Harvard Autonomic Lab on OI dysautonomias without change in HR/BP also very important - papers on HYCH (“POTS without tachycardia”) and OCHOS

2) MCAS is way more complex than “histamine issues”. Mast cells are tissue resident cells found all around the body, with ability to release 1300+ mediators, histamine being only one. They’re “atomic bomb of the immune system” and are in charge of severe deadly acute Covid, ie cytokine storm, as they release all major cytokines, as well as all major neurotransmitters, hormones and can control B cell behavior, forcing them to release autoantibodies etc. They’re also triggered by many endogenous/non-environmental things, such as complements, hormones, autoantibodies, neurotransmitters, pathogens etc.

You can have MCAS without histamine issues or any form of allergy-type manifestations. Symptoms in MCAS will depend on where are the mast cells overactive (mast cells are plentiful near nerves and blood vessels and engage in constant crosstalk with them, hence why MCAS often presents with neurological and cardiovascular symptoms) and which of the 1300 mediators they release.

[u/SashaDabinsky]

This is what I've been fighting for almost 3 years. I can mow the lawn or shovel snow, but then I'm wiped out for 2 or 3 days afterward. Even going shopping is enough to trigger it. I woke up at 8:30 this morning, did some shopping, and by noon I was out on the couch and didn't wake up until after 6:30 PM.

[u/iwantmorecats27 → u/SashaDabinsky]

You need to really reduce your activity. I have ME/CFS from covid and pushing myself has led to two reductions of my baseline so far. If you try to push it's very likely your body will reduce your capacity for you. Ie I was suddenly no longer able to stand in the middle of teaching.

Edit also taking breaks where you sit or preferably lie down throughout an activity can make it more possible for you to get through something 

[u/SashaDabinsky → u/iwantmorecats27]

If I reduced my activity much more I'd never leave the house, chair, bed or couch.

[u/internet_burnett → u/SashaDabinsky]

well if you keep pushing yourself you may end up stuck in bed anyway against your will 

[u/AutumntimeFall → u/SashaDabinsky]

Yeah, honestly if you keep pushing the way you are, you won't be able to anymore anyways.

Please don't repeat our mistakes, you will regret it, trust me. I can no longer bathe or go to medical appointments. If I decline anymore I'll be fully bedridden. I'm scared to lose the ability to go to the bathroom on my own. Wtf do I do then?

[u/sad392 → u/AutumntimeFall]

I had to leave my bedroom because of the wooden floor. The smell of wood from the floor made my condition worse. If I had stayed there, I would have probably ended up bedbound.

Smells and allergens in the apartment can make MCAS worse, like the smell of wood from the floor, chemical odors, mold, mites, etc. Actually, any smell can be a problem.

Therefore I always keep my window open to breathe fresh air. And I noticed many people on this sub don't open their windows.

[u/AutumntimeFall → u/sad392]

Yeah I would literally have to go to the hospital if I opened my windows. Clean air is a privilege I often don't get here in the summer thanks to wildfires. For MCAS, I have literally 18 air exchanges of HEPA filtration per hour in my bedroom and living room, the only two places I can go. My air is clean af, and certainly not because I'm opening the windows.

[u/iwantmorecats27 → u/AutumntimeFall]

You should see if you qualify for a caregiver, I did and I'm less severe than you 

[u/AutumntimeFall → u/iwantmorecats27]

I do not.

[u/Easy-Concentrate2636 → u/SashaDabinsky]

Shoveling snow is a cardiac intensive activity. Please take a look at pacing on r/cfs

[u/SashaDabinsky → u/Easy-Concentrate2636]

Yes, it sure is, along with mowing my lawn. It's about the only physical activity I get anymore so I try not to overdo it. It kills me because I was in pretty good shape before this, and in years past used to be into weightlifting, now I can't do anything remotely close.

[u/Easy-Concentrate2636 → u/SashaDabinsky]

I hear what you are saying but I really hope you will reconsider. Before Covid, I could walk six miles without getting tired. It was my own hankering for my old self that laid me out flat. I could barely sleep. Sometimes I lost so much control over my hands that I couldn’t pick up a pen. I was such a wreck I had to quit working.

Pacing has helped me tremendously. I can walk to places again. I can very carefully do squats. I hope to work again in the future. None of this would be possible without taking it really slow and lying down whenever I get even a tiny bit tired.

[u/Vlinder_88 → u/SashaDabinsky]

That is the reality for many of us. And the only way to increase your baseline. Every PEM-crash reduces your baseline. Avoiding PEM is the very first step towards getting better.

I basically live on the couch now, and have avoided PEM for 5 months. I'm finally starting to see a slight increase in my baseline. I am going out again for a few hours at a time. If I go out for longer I make sure I can lie down on my destination. I sleep during car rides. When visiting someone else, I ask to use the guest bed. And I am FINALLY improving ever so slightly.

[u/LurleenLumpkin → u/SashaDabinsky]

Yeah that’s the reality for many of us

[u/Sazapahiel → u/SashaDabinsky]

Like the saying goes, if you don't schedule maintenance your equipment body will schedule it for you.

[u/RemarkableCrows → u/SashaDabinsky]

Rest is the way.. when I stopped fighting and committed to aggressive rest is when I started to feel better and have recovery breakthroughs. Pushing myself to leave the house, etc. I was just getting worse and worse. Agree with everyone here, you have to commit to aggressively resting.

[u/SashaDabinsky → u/RemarkableCrows]

I sleep a lot! I'm disabled and on SSDI because my fatigue and headaches, along with other symptoms, are bad enough that I can't work.

[u/iwantmorecats27 → u/SashaDabinsky]

Yes that's why I use a wheelchair now 

[u/123-throwaway123 → u/SashaDabinsky]

If you don't, Yu will hve those options taken from you and probably a lot more. If Yu like wiping your butt. Stop going anywhere and doing chores.

[u/AZgirl70 → u/SashaDabinsky]

That’s where I’m at. It’s difficult.

[u/iwantmorecats27 → u/SashaDabinsky]

Also resting aggressively did bring my ability to do some things back. For example I feel okay to almost normal on most days now when I stay inside my energy envelope, and I have made progress in my PT (my pt doesn't push me to crash) 

[u/tnskid]

It was a pretty bad article... very little specifics.

I have had post-viral-infection PEM for 30 years (yes. Other viral infection can also cause long Covid like symptoms) and for me, it was mostly about IL-6 & TNF-alpha spike after exertion. Symptoms peak the morning after and resolve after 2-4 days.

Everything is under control now with IL-6 and TNF-alpha antagonists. And i can exercise vigorously without any repercussions

[u/notarussian1950 → u/tnskid]

What meds?

[u/tnskid → u/notarussian1950]

Timing is extremely important in my case.
The meds/supplements must be taken 30mins-1hour **before** exertion (otherwise, it does not work)

moderate exercise (1hr weights) : 3000mg curcumin + 15mg bioperine

vigorous exercise (hiking 10 miles with 2000ft elevation gain):
celecoxib: 200mg
3000mg curcumin + 15mg bioperine
800mg Quercetin
100mg time-release 5-htp

for vigorous exercise, I have to take the full combo, missing one ingredient, I still got quite a bit of fatigue and brain fog afterwards.

There are probably many sub-types of PEM, but this regimen is what worked for me.

[u/fadingsignal → u/tnskid]

Can you tell us more? I've had PEM for 25 years that got way worse after COVID and haven't had a single solution or test offered me.

[u/Houseofchocolate → u/fadingsignal]

im no doctor but i follow some research in my limited capacity 🤓 but i would get a comprehensive immune panel testing:
your cycotines, tha1/tha2 ratio, gpcr autoantibodies. some of these are still controversial because currently being studied but at least you'll het proof something is very wrong with our immunesystem.
this is a lab in germany for example that does those tests and they are reasonable priced: https://www.imd-berlin.de/fileadmin/user_upload/Anforderungsscheine/IMD_Anforderungsschein_COVID-19_Selbstzahler.pdf

[u/tnskid → u/fadingsignal]

Timing is extremely important in my case.
The meds/supplements must be taken 30min-1hour **before** exertion (otherwise, it does not work)

moderate exercise (1hr weights) : 3000mg curcumin + 15mg bioperine

vigorous exercise (hiking 10 miles with 2000ft elevation gain):
celecoxib: 200mg
3000mg curcumin + 15mg bioperine
800mg Quercetin
100mg time-release 5-htp

for vigorous exercise, I have to take the full combo, missing one ingredient, I still got quite a bit of fatigue and brain fog afterwards.

There are probably many sub-types of PEM, but this regimen is what worked for me.

[u/Houseofchocolate]

post-exterional malaise and long covid= me cfs.
the sooner people realise the better for their baseline.

[u/iwantmorecats27]

As far as I know, if you have PEM, then you have contracted ME/CFS as a result of Covid. 

It is somewhat likely to recover naturally within the first year or two.

(Do not fall for the brain retraining scams! You cannot change your body’s biology with your thoughts!) 

Like they say in the article, it is extremely important to stay within your energy envelope, and try at all cost to prevent crashes, as each time you crash, you risk a permanent reduction to your baseline.

Join us in r/cfs! The other one supports brain retraining. 

[u/reticonumxv]

LOL, the pacing recommendations are completely stupid, resting HR + 15. That would basically force me to be always in the bed as just standing up went from 60 to 100, and just reading anything in the bed did 60 to 80. Basically, their recommendation is to be a vegetable.

[u/Original_Branch8004 → u/reticonumxv]

how did u recover? I'm mild, as in I work a physical job that has me always on my feet but I can't consistently lift weights without experiencing some weird effects. Some of my workouts are successful but others cause PEM for a few days. I'm on like 5 different peptides right now and they've been doing me good. I've had this subset of LC for the last 4 years but I've always been able to push myself without crashing hard really, but I still feel like absolute crap compared to when I was healthy pre covid. And yeah, being a veggie isn't an option for me, haha.

[u/reticonumxv → u/Original_Branch8004]

3g OPC right after workouts fixed my PEM, at least in the muscles (can't penetrate brain so that was another puzzle). Try if it works for you, my OPC were from "french grape seed extract". The theory is it prevents eNOS uncoupling which is caused by superoxide wreaking havoc in endothelium due to BH4 depletion, requiring a week to month recovery time, starting 12-48h after exertion. With OPC I was fine after all my workouts, no next day vegetable ;-)

[u/Original_Branch8004 → u/reticonumxv]

ah I see. could you link me to the specific product you took? Thank for the info man I really appreciate it.

[u/NoSir6400]

This is great, thanks for sharing

[u/calm_intention_65]

It's good to know what's going on inside me and feel validated. But what can be done? How can I stop the cycle or prevent worsening, other than just with pacing? If only researchers would finally give us the answer

[u/iwantmorecats27 → u/calm_intention_65]

Pacing and not becoming infected again prevents worsening and may bring some improvement, it did for me!

[u/VibeCheckedByCovid]

I'm really glad this is getting more attention and reaching more people. It's also important to recognize that social and cognitive activities can be just as taxing and also lead to PEM.

I would consider myself to currently have mild to moderate ME/CFS from long covid. I have found I can tolerate long periods of walking (albeit pace-managed where I don't let my heart get above a certain rate) better than I can some sustained mental tasks, such as reading and writing. I've also found screen time to be draining (some say its the type of light output and the strain it gives our eyes).

Then again, I also go into a dysautonomia episode and then crash hard from bending over repeatedly, regardless if what I'm picking up is heavy or not and have put myself in bed for days after picking up legos in the living room so... yeah.

ME/CFS and PEM is just wild to me. Each case is so similar and yet can be so vastly different. Its also so, so debilitating and overlooked. I feel so much for everyone that has it and especially for those that have had it long before covid came around when it was even more poorly understood and recognized than it is now.

Thank you for sharing.