Review Towards an understanding of physical activity-induced [PEM]: Insights into microvascular alterations & immunometabolic interactions…, 2024, Haunhorst+

Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome
Haunhorst, Simon; Dudziak, Diana; Scheibenbogen, Carmen; Seifert, Martina; Sotzny, Franziska; Finke, Carsten; Behrends, Uta; Aden, Konrad; Schreiber, Stefan; Brockmann, Dirk; Burggraf, Paul; Bloch, Wilhelm; Ellert, Claudia; Ramoji, Anuradha; Popp, Juergen; Reuken, Philipp; Walter, Martin; Stallmach, Andreas; Puta, Christian

BACKGROUND
A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated.

PURPOSE AND METHODS
In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM.

RESULTS
Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.

Link | PDF (Infection) [Open Access]

 

I've just started reading this and there's a subtlety in it i appreciate. They distinguish exercise intolerance from PEM:

Importantly, PEM is clinically often accompanied by fatigue and profound exercise intolerance. Yet, while being pathogenically connected, they constitute separate entities of the post-infectious disease manifestations. In fact, exercise intolerance refers to the inability to uphold acute exercise due to lack of energy, or rapid development of palpitations, tachycardia, or breathlessness. On the other hand, PEM describes an inadequate delayed regulatory response that elicits the aggravation of symptoms such as fatigue, pain or cognitive impairment and a decrease in the physical capacity level.

I suspect this is something we should talk about more. Are you more affected by being tired when exerting, or later?

Some people find it impossible to stand up and do anything (e.g. I read about people whose legs burn if they try to walk), others find it easy to do things and therefore very easy to overdo things. I'm wondering if this is correlates exactly with the differences between mild and severe or if it's a separate disease dimension. If the latter, finding people with low exercise intolerance but a heavy PEM onset could be the people in whom the PEM signal is strongest.

 

I'm very severe, and I find it extremely easy to overdo things. Exertion intolerance (which for me is legs feelings so heavy that it feels like they're pulling painfully on my hips even though I'm laying flat; arms burning and muscles shaking; breathlessness and a crushing sensation on my chest; tachycardia, darkening vision, and a whistling tinnitus, like when you've been hit) only appears if I'm in PEM, but if I am in PEM then it's instant upon exertion. In fact, even though I have not stood up in almost 3 years, if I'm not in PEM, my legs get antsy and it takes all my mental concentration to not slide them out of the bed and press my feet down on the floor. I did that last week and am now paying for it with all kinds of strange sensations (legs full of static, filling up with blood and heat, etc.)

I distinguish this type of PEM from the constant symptoms I experience because this type is episodic.

 

I'm fairly active, a half hour brisk walk every day and about an hour total each day. Fast walking is ok but shopping walking or standing is a problem pretty quickly.

My current limit for any activity or outing is about 2 hours. After that I go downhill rapidly.

When when I was teaching 15 years ago, after two hour long classes I'd lie on my office floor for an hour. After I got home I'd lie flat on the deck for an hour, usually falling asleep. At the time I was drinking three pots of coffee a day.

This was well before cerebral perfusion was being discussed. As long as I stick to the two hours on, an hour or laying completely flat, I'm pretty good.

When I over do it, say to attend an all day function, I know I'm going to have to pay for it with zero energy day (s). My recovery strategy is to basically lie in bed for as long as it takes. Often then I get out of bed for a few minutes at a time, only to discover that I just have an uncomfortable urge to go lie down.

When I drive my partner to the airport for his weekend trips, after the hour drive it often takes me two days to recover, just in time to pick him up again and be exhausted for another two days.

Viagra makes a difference, often for 24 hours. The length of time may be due to taking ritonavir, which is often used as a booster because it slows the liver clearing the Viagra. Coming from the gay world, I've also considered amyl nitrate, though I suspect the effects wouldn't last long.

 

You sound similar to me in terms of activity limits. Are you able to work?

 

I wonder if it's more complicated for some people.

I can only walk a few yards—my legs feel full of lead and will eventually buckle if I don't sit down, and I have significant OI. As soon as I rest my legs burn, and it usually keeps me awake half the night.

But on other measures I'm not severely ill. I almost never spend time lying down except overnight, especially as the burning pain's at its worst when horizontal. And although I'm not fit to work, I can usually get out of the house for a couple of hours once or twice a week.

I find it easy to overdo some things—practising music, talking to a friend, swimming when I'm able to, etc—but I've so little capacity for walking and standing that there's effectively no level of activity minor enough to mean I don't overdo it.

 

I had to go on disability ten years ago. There were lots of signs of problems but I had quite a few coping strategies. At the time there wasn't much good information so many strategies were just figuring out what worked.

In the computer lab, often two or three hours long, I'd pull up a chair to help a student, or sit on the floor beside them.

In the industry at the time programmers started to get coding assistance from "integrated development environments". Rather than writing code on the blackboard I would sit at a desk, display my laptop screen using a projector and show them how to code. It was really innovative at the time. In the second term, when I had to stand to draw diagrams on the board for most of the class I was noticeably exhausted at the end of the day.

It reached a point where I spent the whole weekend in bed and still hadn't recovered by Monday morning. Even so I was riding my bike to school, then to the gym later in the day.

For a long time I thought I must have ADHD because watching TV in the evenings I kept popping up to do some inconsequential task.

When I was lying down I would write code or compose emails in my head but when I got up to sit at a desk and write it down my mind would be totally blank. It was extremely frustrating and still happens.

Again, much of this points to cerebral perfusion.

I'm in the gradual onset category. I tend to think that many people have similar coping strategies which appears as sudden onset when they have completely exhausted themselves.

After I went on disability I spent a few years mostly lying in bed. At one point I learned to get much better by allowing myself to stay in bed as long as it took, whether that was hours or days. I taught myself pacing and have a pretty constant and mostly unvarying routine. It allows me to substitute activities and know when to go lie down.

For many years I tried pretty much any drug that might have been beneficial. I discovered that pretty much any therapy (even a holistic things like a spa day) acted as "stimulants" and had consequences. Now I avoid most remedies and just go lie down completely horizontally.

 

I was that latter group I would have thought when I’ve been less unwell.

I had to live a life of PEM and rolling PEM and was firmly moderate but with constant pain in legs and just cumulating exhaustion (despite sleep as soon as not in work and some home days I just could not function until x time and forced thru si couldn’t actually do five normal days at all ). But had to take a week off every six weeks to basically sleep solidly or I’d have lost my job as I’d have ceased to really function that blag.

now I’m severe in bed bound and unable to sit up for most of the time - sitting up time is one way if distinguish if I had some PEM vs the few times properly rested. But I still when I have medical appointments walk short distances (wheelchair alternatives when being dropped off in car I’m considering as make that too much eg walking round different hospital depts and I had PEM I’m not sure I’ll recover from ie permanent deterioration thing, sane with two flights of stairs)

I’ve learned my physical in very planned only every few weeks max ‘looks’ less ill than I am (conversations are too much) but causes great PEM. However if you took this as % to prior self then my physical is absolutely spot on - walking 200m would have nothing to me in prior life.

so my point is there are added complications when I try to think through that one.

but I always thought of myself as more PEM y hence the chronic fatigue not making sense because it being the pow hit of ‘why can’t I even wake up and move today’ shock. Now I’m severe that PEM is still the case but I have very few hours in the week of ‘do’ and I’m bedbound very much and just anything at a set time whether it’s a call I’d have to plan (and even then you can’t plan others noise or sleep or pain) to have a chance of not feeling a risk of being so ill I could be led by the nose.

on the other hand whilst I’ve engaged all sorts to get going for work the leisure stuff is insightful because slowly that went down because I had to explain that turning up to a party with flu is the equivalent for me when people (people are awful with this therapists mindset they’ve been taught) say ‘you’ll enjoy’ or ‘have fun’ when trying to get them to have some empathy and understanding of what they were suggesting

it’s funny watching the brain crunch if most and I think their bigotry is just then having chosen to and been brainwashed to switch off that curiosity of empathy module. It’s so obvious because when you come across the few not yet blighted by it then it’s so much more straightforward. It’s hilarious watching those bigoted people ‘try’ the best they can do is be quiet and not listen as they think that’s ’being like a counsellor because they just want to get it out’ - another couldn’t get more of a misinformation of the most important and seemingly obvious facts of human life and nature.

I mention it because that makes adjustments impossible to get because too many have been taught to passive aggressively ‘take what they need’ and manipulate the interaction to get it and reframe it. People like this make life inaccessible in total to me, whereas when you come across a normal who isn’t blighted by it then important things are. Because the former can’t help but undermine and unpick everything as they’ve been taught not to respect and it’s very slippery to deal with.

 

Seems all very speculative (and that is probably an euphemism).

 

Merged thread

Article

https://link.springer.com/article/10.1007/s15010-024-02386-8

Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract

Background

A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated.

Purpose and methods

In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM.

Results

Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.

 

I think this confuses the reduction in performance on CPET with the actual symptoms of PEM, which are too delayed to be explained by things like lactate. There may be some interesting content but the abstract looks underwhelming.

 

A condensed bombardment of data.
Too overwhelming for my brainfog.