Comparing acute sickness symptoms with ME/CFS

[forestglip]

I thought it might be worthwhile to have a discussion comparing and contrasting the symptoms of an acute infection (a week or two of flu, cold, staph, etc.) and ME/CFS. Viral persistence is often mentioned in discussions of mechanism theories. I personally think there's a good chance ME/CFS is literally a "long" infection. Maybe something is wrong with the immune system that allowed it to become "long", but just in terms of symptoms, simple infection might be able to mostly explain those.

This paper did something like this comparing and contrasting:

A narrative review on the similarities and dissimilarities between [ME/CFS] and sickness behavior, 2013, Morris et al

Here's their table comparing the symptoms of each: Link

There are a lot of similarities in symptoms:

cross-sectionally there is a phenomenological overlap between sickness behavior and ME/CFS, both presenting with malaise, hyperalgesia, fatigue, exhaustion, sleepiness, failure to concentrate, and sometimes mood disturbances.

I think one of the biggest questions to drill down on is, does PEM occur in acute illness in otherwise healthy people? If it does, I think that'd be strong evidence that the two conditions are related (and evidence of what PEM is). In that case, the difference between the two would be some unknown factor that allowed the pathogen to hide away somewhere.

If acute illness doesn't include PEM, that doesn't necessarily mean ME/CFS is not pathogen persistence. In that case, maybe the reason an infection becomes a "long" infection is precisely because of PEM: someone with ME/CFS's immune system gets all wonky after exertion, which allows the pathogen to spread and take root somewhere, and this doesn't occur in healthy people because exertion doesn't mess with their immune system.

The paper says:

Post-exertional malaise following mental and physical activities, a characteristic symptom of ME, probably also occurs during sickness behavior.

I mean, most everyone has been sick, and we don't really think of PEM as being a part of it. But I think there are potential explanations for that.

First, the short duration of acute infections. It's only a week or two, where someone's energy levels and other symptoms are already rapidly changing over only a few days. If someone went for a run while sick, then got even worse two days later, I can see how they might think their illness just got a bit worse, as illnesses sometimes do, and it had no connection to the running. They don't have the advantage (ha) that people with ME/CFS do, where they experience PEM over and over and over, and can start to detect a pattern of exertion causing it. From what I recall, it took me quite a long time to realize fatigue randomly getting much worse was tied to something like a long walk two days before. Because why would I ever think that when I've been told my whole life that exercise can only be healthy.

Second, maybe they do make the connection that exercise caused them to get worse after a day or two, but they don't think of it as "PEM". Maybe they think of it as "I went for a run, and that weakened my immune system, so the infection got worse." The symptoms might be similar, but doesn't seem obviously to be the same as PEM, because in acute infection the "effect" is "worse infection", with its expected increase in fatigue and other symptoms, while in ME/CFS, the "effect" is "worse fatigue and other symptoms". The lack of infection in ME/CFS to explain things might get in the way of seeing the similarities in symptoms.

 

[forestglip]

Data that would be useful for this would be how bed rest affects the duration/severity of a sickness. That's the commonly prescribed advice from our doctors and parents. "Rest so that the body can heal." If this advice is based on a real effect, I think that's basically evidence of PEM: if you get up and exercise, your sickness will get worse.

I found an observational study from 1936 (!) that looked at the effect of delaying bed rest on acute illness: The common cold and the effect of rest in bed on its course, 1936, LeBlanc et al

They compared nurses hospitalized for "common cold" that reported that they started bed rest within 30 hours after the start of their infection symptoms, with those that waited longer.

Being an observational study, there are of course confounders that make it difficult to infer causality, some of which they go into:

A patient was admitted to the hospital when she had fever, a complication, or general systemic symptoms such as fatigue and muscular aching. This fact gives rise to the question as to whether the group with delay in going to bed were suffering from a milder in- fection which was slower in developing to the point where the symptoms were such that they would justify hospitalization. It is our belief that the infections were of the same type and that these individuals went about their regular duties with fever and systemic symptoms some time before reporting for medical advice. The other type of person reported immediately when any systemic symptoms became apparent. This impression is supported somewhat by the time distribution of admissions in the two groups. The similarity of this distribution, shown in figure 1, suggests that the causative agent is identical for both groups, and from an epidemiological stand- point this implication seems reasonably strong.

The remaining possibility is that the delayed group after exposure to the same causative agent as the other group had enough so-called resistance or immunity so that there was an extended incubation period which manifested itself in a prolongation of time before these persons were sick enough to be confined to bed. We can neither prove nor disprove this point.

I don't see how the limitations they list could explain illness being so much worse in the delayed group. It seems they would explain the opposite. But I'm sure there might be reasons people who waited longer to rest got sicker. One possibility is maybe people who are unhealthy and prone to severe complications are unhealthy because they are worse off socioeconomically, and thus would work longer to not miss out on the money. These are all nurses, so I assume their incomes are similar, but maybe some have wealthier family which allows them better healthcare and diet, and less need to work through a sickness.


Nevertheless, the outcomes at least support the possibility that not resting during a cold leads to worse illness.

Non-delayed group entered the hospital and commenced bed rest an average of 18.8 hours after onset. Delayed group entered hospital 138 hours after onset. They measured days of fever, days in hospital, days off duty, total length of illness, loss of weight, and number of nurses with complications. All were worse in delayed group, although fever and weight loss were not significant. Strikingly, the delayed group had over five times the prevalence of complications.

By the term complication is meant acute sinusitis, acute otitismedia, peritonsillar abscess, acute bronchitis and the pneumonias.

67.4 per cent either had on admission or developed during the period of hospitalization one or more complica- tions. The corresponding figure for the group who went to bed with- out delay was 11.3 per cent.

I'll see if there are any more bed rest studies. I assume an RCT wouldn't be approved as ethical, but who knows.

 

[Hoopoe]

My first PEM episode was hard to distinguish from the initial phase of a mild infection, where the fever hasn't yet started but you can feel that you're sick.

In September I probably had covid and it took a few days to realize it was an infection and not just ME/CFS. when the infection / immune response peaks and fever appears, it's clearly distinguishable from ME/CFS, but before that it can pass for ME/CFS.

 

[forestglip]

when the infection / immune response peaks and fever appears, it's clearly distinguishable from ME/CFS, but before that it can pass for ME/CFS.

What exactly makes it distinguishable? Just the fever or something more?

 

[Kitty]

My first PEM episode was hard to distinguish from the initial phase of a mild infection, where the fever hasn't yet started but you can feel that you're sick.

In September I probably had covid and it took a few days to realize it was an infection and not just ME/CFS. when the infection / immune response peaks and fever appears, it's clearly distinguishable from ME/CFS, but before that it can pass for ME/CFS.

Similar for me, I can only be sure PEM isn't a virus when it stops at sore throat, swollen glands, and a slightly runny nose. It never causes sneezing, coughing, sinus pain or earache, and while PEM sore throat's annoying, it isn't as painful as some colds.

But while it seems plausible that some of the 'bleuurgh' in PEM is caused by the same immune factors as the response to a respiratory virus, I'd argue it's important to regard it as different for now. If researchers make assumptions, they could completely miss the most important clue.

 

[Hoopoe]

What exactly makes it distinguishable? Just the fever or something more?

The fever and the symptom profile and intensity. It just feels different. I wonder if the "feels like the beginning of an infection" is a clue that the innate immune system is a key player in ME/CFS.

 

[forestglip]

Surprisingly, I found an RCT of bed rest for tuberculosis. Also an old paper.

Bed rest in the treatment of pulmonary tuberculosis, 1956, Tyrrell et al

They admitted every other patient who presented with TB to a hospital for 3 to 6 months bed rest, and instructed the rest to continue normal exercise.

In May, 1954, it was possible to admit to sanatoria only some of the patients with pulmonary tuberculosis in Glasgow, and the remainder were of necessity treated as outpatients. From a public-health viewpoint this situation was clearly unfortunate, but it did offer an opportunity of assessing the therapeutic value of bed rest. It was accordingly decided to admit to hospital every alternate new patient in the 1B c>rtllern area of the city and to treat the others as ambulant outpatients. The criteria for acceptance into the trial were that the patient (1) had active pulmonary (2) was aged 14-54, (3) was not living in lodgings, and (4) was ambulant when first seen. Those allocated to inpatient treatment were admitted to the sanatorium within two weeks of diagnosis and were kept on strict rest in bed.

Altogether 141 patients have completed three months’ treatment, and 94 of these have completed six months’ treatment.

The conclusion was basically they found no differences in outcomes.

Despite the adverse environmental factors in the out- patient group, examination of the position after three months’ treatment showed no significant difference between the response of the two groups assessed by fall in E.S.R., sputum conversion, extent of clearance of lung disease, and cavity closure. It is true that the inpatients as a group gained more weight than the outpatients ; but this must surely be regarded as reflecting physical inactivity rather than regression of disease, because, as is generally agreed, weight gained by patients in a sanatorium is usually rapidly lost when they resume outside activities.

A few patients in both groups have been assessed after completion of six months’ treatment. Here again there is little difference in the general response ; but cavity closure was commoner in the inpatients. It would, of course, be unwise to reach any firm conclusion before greater numbers are compared, but it would not be surprising if further experience confirmed this trend. Apart from any question of toxaemia or activity of the disease process, there is possibly a mechanical factor in cavity closure which is exploited in many centres by, for example, reversed postural drainage.

 

[Mij]

I think one of the biggest questions to drill down on is, does PEM occur in acute illness in otherwise healthy people?

I experienced delayed muscle weakness/fatigue in my legs from Covid infection after going out for my regular power walk after I felt recovered. It did not affect my cognitive energy. It was not the same experience as ME/CFS delayed full body toxic PEM.

 

[Mij]

I should also mention that in early 2000 when HHV6 and EBV was reactivated I had to rest for 2.5 months. I went out for a short run after I felt recovered and the next day the delayed PEM completely changed my baseline for good. This was when OI set in and I've had it ever since.

 

[Sly Saint]

tuberculosis

Convalescence for TB was the norm back in the day;
see film 'Twice round the daffodils'

 

[forestglip]

Another two that found no benefit from bed rest in tuberculosis:

Is cavity closure in pulmonary tuberculosis influenced by bed-rest?, 1960, Wynn-Williams et al

A group of 62 patients with tuberculous cavitation caused by drug-sensitive organisms was treated with antituberculosis drugs and allocated at random to regimes of bedrest until cavity closure, or exercise. The condition of each group of patients was assessed at six months. No difference was found between the two groups in the time taken to cavity closure, sputum conversion, and reduction of the ESR. Further assessment after 12 months showed similar results between the two groups. Patients in the ‘rest’ group were over twice as long off work as in the ‘exercise’ group.

I can't access this one, but the article below it describes the results:

Late Results of Modified Bed Rest in Active Uncomplicated Minimal Pulmonary Tuberculosis, 1953, Mitchell

Bed rest in tuberculosis

At Trudeau Sanatorium MITCHELL has studied the results of bed rest in minimal pulmonary disease by analysing 589 cases of limited uncavitated tuberculosis which were treated between 1927 and 1946. As the mortality-rate was low-5% in twenty years-he used the relapse-rate to measure the effect of treatment, which basically consisted in rest in bed for all but three or four hours a day. The duration of rest appeared to have no effect on the frequency of relapse. Thus, of 310 patients who were in bed for only one or two months, 22-3% relapsed within five years ; while of 109 who had six or more months in bed 22% relapsed. As would be expected, the prognosis was significantly affected by the extent of the disease ; but this could not explain the lack of correlation between duration of rest and relapse, for it did not appear to have been an important factor in determining the duration of rest. Moreover, those who spent the shortest time in the sanatorium seemed to have done no worse than those who spent the longest.

MITCHELL then investigated the late results
in patients with pleural effusions.2 The relapse-rate within five years of discharge was found to be influenced by the presence of minimal pulmonary disease and by its extent. But, once more, the duration of bed rest or stay in the sanatorium had no obvious effect.

An RCT of bed rest in infectious mononucleosis also found no benefit:

INFECTIOUS MONONUCLEOSIS. 2. RELATION OF BED REST AND ACTIVITY TO PROGNOSI, 1964, Dalrymple

Ninety per cent of a consecutive series of
131 patients with infectious mononucleosis recovered completely within six weeks; even
fatigue had disappeared by this time. Furthermore, those allowed activity as desired during their illness and convalescence improved more rapidly than those kept at strict bed rest during the acute stage of the disease. Strict bed
rest or prolonged limitation of activity is justified only in unusually severe cases of infectious mononucleosis or in the presence of severe complications.

No benefit found in a review focused on rheumatic fever:

Role of bed rest in treatment of rheumatic fever; review of literature and survey of current opinions, 1957, Duman et al

In a review of the literature and a questionnaire survey of specialists in rheumatic fever, no objective proof was found to indicate that strict bed rest is necessary for a satisfactory convalescence in acute rheumatic fever.

----

I think there is a possibility that bed rest has no benefit if the patient doesn't desire to rest. Maybe only if someone is very tired from an infection and is forced to exercise/work will they have a worse outcome.

For example, the mono study above said the non-bed rest group did activity "as desired", so maybe their body didn't require rest to heal.

 

[forestglip]

Convalescence for TB was the norm back in the day;
see film 'Twice round the daffodils'

Yes, I was wondering why I'm seeing so many papers talking about bed rest in TB, but almost none in other infections.

 

[forestglip]

Four references in this study about exercise worsening health during an acute sickness, three of which are in rats.

Acute Infection: Metabolic Responses, Effects on Performance, Interaction with Exercise, and Myocarditis, Friman et Ilbäck, 1998 (thread)

One such infection is acute viral hepatitis, where controlled studies have shown no adverse short or long term effects of exercise of various intensities during the early course of the disease (13,60,72). Conversely, in poliomyelitis, exercise may be hazardous and promote the development of palsies (for a review. see ref. [67]). In patients suffering febrile respiratory infections, a mild activity programme of letting the patient out of bed every half hour during waking hours. i.e. "G-training", throughout the entire febrile course resulted in less blood volume reduction and less of an aerobic capacity decrease than conventional bed rest (41).

The effects of strenuous exercise during acute febrile infections have been studied in experimental animals. In one study of a prototype, non-myocarditic, bacterial infection (tularemia) in the rat, it was shown that exhaustive exercise during the febrile phase evoked an anabolic response in striated muscle (myocardium) that limited the infection-associated muscle catabolism (27). Consequently, the exercised rats performed better than the resting controls at the end of the infection. The frequency of serious complications, such as spread of the infection to unusual sites, was however higher among the exercising animals. In another exercise experiment, where the effects in one bacterial (tularemia) and one viral (influenza) in- fection, with similar lethalities at rest, were compared, no beneficial effects of exercise were observed in influenza. In fact, in contrast to the observation in tularemia, exhaustive exercise during influenza evoked no anabolic response in muscle and exercise was associated with increased lethality (49). Likewise, lethality was increased with exercise in rats suffering Streptococcus pneumoniae infection (50).

All animal experiments on non-myocarditic bacterial and viral infections that we are aware of show that strenuous exercise during the febrile phase may be hazardous. For evident ethical reasons, similar experiments in humans are not feasible. Thus, there is no scientific basis for not recommending rest in the acute phase of all such infections.

 

[forestglip]

There are some researchers, like John Chia and Maureen Hanson, that think chronic enterovirus infection plays a role in ME/CFS, so research on poliovirus, an enterovirus, could be useful.

Looking at the reference from the study above for exercise worsening polio. It's a book available to borrow on Internet Archive:

Exercise Immunology by Bente Klarlund Pedersen, 1997

A lot of this looks like it could be interesting in the table of contents, but I'm just looking at chapter 9, Exercise and Infection.


On strenuous exercise during poliovirus infection leading to increased paralysis:

Despite many sporadic reports on vigorous exercise preceding paralysis, these did not provide any information on a possible causal relationship. However, a striking phenomenon reported by Howe and Bodian stimulated Russell to investigate the influence of exercise statistically. Howe and Bodiad made the interesting observation that if the anterior horn cell was engaged in regenerating its neuron, that is, if the peripheral nerve originating in these cells had been sectioned a few days previously, these anterior cells were then quite immune to experimental infection with viruses. Based on this, it was by no means impossible, that physical activity at a certain stage of disease might alter the motor neuron physiology in such a way as to influence its susceptibility to infection.

Russell studied the effect of physical exercise during the preparalytic period. In total he reported 100 cases of poliomyelitis studying the initial symptoms in details. The patients were questioned about their early meningitis-like symptoms consisting of pain in the head, neck, dorsal, lumbar or sacral spine. Physical activity of any kind during the paralytic stage increased the danger of severe paralysis, whereas complete physical rest during the whole of the preparalytic stage protected the patient from severe paralysis.

These observations concerning poliomyelitis were later cofirmed in other epidemiological studies, as well as in experimental animal studies.

Hargreaves analyzed 30 cases of poliomyelitis and confirmed the previous findings by Russell that physical exercise in the preparalytic phase was associated with grave prognoses. Furthermore, he suggested that severe mental stress such as driving a car over long distances, appeared to be equally disastrous.

In regards to hepatitis infections, exercise has not been found to be harmful.

A couple mice studies found exercise caused increased mortality or myocardial damage from Coxsackie B. There was also some discussion about an unexplained cluster of increased deaths in orienteers; a very speculative claim was made about this being due to exercise worsening Chlamydia pneumonia infections.

A few other animal studies looked at different infections, including type I pneumococcus, Toxoplasma gondii, influenza, Salmonella typhimurium, Streptococcus pneumoniae and Francisella tularensis. Of these, exhaustive, but not moderate, exercise in influenza increased lethality, and exercise after infection with Streptococcus pneumoniae or Francisella tularensis increased lethality, but the rest of the infections weren't worsened by exercise.

The book talks about increased rate of upper respiratory tract infections in competitive athletes, but this is still a very contested claim. The following paper is a debate between those who do and don't think exercise increases rate of URTI in athletes:
Can exercise affect immune function to increase susceptibility to infection?, 2020, Simpson et al

This could be interesting:

Friman and Ilback stress the point that those examples (poliomyelitis and myocarditis), where exercise seems to worsen the clinical disease, are typified by the location of the infectious process within a tissue or organ that is mechanically or metabolically active as a result of exercise.

In the same vein, a much earlier review on exercise and polio talked about the observation that trauma or exercise to a certain body part during infection seemed to make it more likely for that body part to become paralyzed. Intros for those sections:

Paralytic Poliomyelitis, Russell, 1949

There are a few reported cases of poliomyelitis in which local trauma appeared to determine the site of maximum paralysis (see Levinson et al., 1945). In such a case, for example, poliomyelitis occurring soon after an arm fracture would lead to paralysis affecting chiefly the fractured arm. This type of case, infrequent though it is, raises the possibility either that peripheral trauma provides the virus with easy access to the neurones or that it modifies the physiology of the spinal cord cells of the segments concerned in such a way as to make them more vulnerable to the virus.

There have been many reported instances of the paralysis of poliomyelitis being worse in those muscles which were most exercised at the onset of the illness.

-------

Now I'm wondering if there might be any data on physical activity during acute COVID infections, and whether it is associated with increased incidence or severity of long COVID.

 

[Kitty]

There's also the apparent—and curious—link between motor neurone disease and very high levels of activity.

MND may not be infection-associated, but it seems to affect people who're particularly fit and active. Much the same has been said about ME/CFS, though of course it's a totally different beast. But ME/CFS is much more common than MND, so any link ought to be easier to study as part of a prospective project.

 

[forestglip]

There's also the apparent—and curious—link between motor neurone disease and very high levels of activity.

MND may not be infection-associated, but it seems to affect people who're particularly fit and active. Much the same has been said about ME/CFS, though of course it's a totally different beast. But ME/CFS is much more common than MND, so any link ought to be easier to study as part of a prospective project.

Thanks, I'd never heard this. Found this BBC article from 2021:

Motor neurone disease: Intense exercise increases risk, say scientists

Overall, around one in 300 people will develop motor neurone disease.

It affects people's ability to move, talk and even breathe as the motor neurones that carry messages from the brain to the muscles fail. It can dramatically shorten people's lives.

There has long been a connection between exercise and the disease, but whether it was a genuine "cause" or just a "coincidence" has been the source of fierce debate.

Studies in Italian footballers have suggested rates up to six times higher than normal. Athletes including Rob Burrow (rugby league), Stephen Darby (football) and Doddie Weir (rugby union) have all spoken openly about the disease.

The researchers analysed data from the UK Biobank project, which has detailed genetic samples from half a million people.

They used a technique called Mendelian randomisation to turn that data into an experiment, and showed people whose DNA makes them more likely to do strenuous activity were more likely to get MND.

The study, published in the journal EBioMedicine, also showed:

• many of the genes known to increase the risk of motor neurone disease change their behaviour in response to exercise
• people with the most common mutation linked to MND develop the disease at an earlier age if they exercise strenuously

Here's the study, which appears to be specifically about ALS, a type of motor neuron disease:
Physical exercise is a risk factor for amyotrophic lateral sclerosis: Convergent evidence from Mendelian randomisation, transcriptomics and risk genotypes, 2021, Julian et al

 

[poetinsf]

I think one of the biggest questions to drill down on is, does PEM occur in acute illness in otherwise healthy people?

You can put a flu/cold patients on 2-day CPET test and see if the performance decreases on the second day. No reason why you can't. It may need to be controlled for the worsening of infection on the second day though. Perhaps you can do that by comparing the viral load, etc. People who are sick with typical flu/cold should do fine with 10-100W in 10 minutes, I'd think.

Or, you can ask Michael Jordan. He once played full 60 minutes during a championship game with flu.
In my personal experience, moderate exercise during flu/cold, when I can muster, does not make the symptoms worse the next day.

If acute illness doesn't include PEM, that doesn't necessarily mean ME/CFS is not pathogen persistence. In that case, maybe the reason an infection becomes a "long" infection is precisely because of PEM: someone with ME/CFS's immune system gets all wonky after exertion, which allows the pathogen to spread and take root somewhere, and this doesn't occur in healthy people because exertion doesn't mess with their immune system.

I don't know what you are trying to get to. We are talking whether acute infection in healthy people includes PEM, right? It's a separate topic whether ME/CFS PEM is caused by viral persistence. It isn't, if you ask me. Viral load change is organic and has very wide variance. PEM, on the other hand, is often extremely precise in moderate/severe ME/CFS cases. It's very unlikely higher viral loads caused by exercise is the cause of PEM.

In any event, you should be able to test that hypothesis by checking the viral load before/after exercise. But then, the test is unlikely turn up anything if the patient was negative for virus to begin with.

[edit: added the last paragraph]

 

[forestglip]

You can put a flu/cold patients on 2-day CPET test and see if the performance decreases on the second day. No reason why you can't.

I think researchers may consider this kind of testing to be unethical. I'm guessing because the tested hypothesis would include increased risk of death from infection, among other things. From the Friman study a few posts up:

All animal experiments on non-myocarditic bacterial and viral infections that we are aware of show that strenuous exercise during the febrile phase may be hazardous. For evident ethical reasons, similar experiments in humans are not feasible.

---

I don't know what you are trying to get to.

Basically, it seems like the most obvious hypothesis is ME/CFS is long infection, and that PEM is viral load increasing due to exertion, and I'm astounded that I haven't seen this PEM idea mentioned even a single time in research. (Edit: Not that I've searched that deeply. If anyone has seen something like this, I'd love to know.)

The three main reasons I think so, which I wrote in another thread:

The reasons being the profound symptom similarities between [ME/CFS and acute infection], as well as the obvious connection to infection that ME/CFS has. But most of all, I think a replicating pathogen is the most obvious explanation for PEM, as it explains the delayed onset (time for the pathogen to replicate)

---

We are talking whether acute infection in healthy people includes PEM, right? It's a separate topic whether ME/CFS PEM is caused by viral persistence.

The connection is that if exercise causes increased viral load during acute infection, and if it is found that ME/CFS is at least partly a "long" infection, the obvious question is if exercise also causes increased viral load during ME/CFS, which could explain PEM.

Viral load change is organic and has very wide variance. PEM, on the other hand, is often extremely precise in moderate/severe ME/CFS cases.

Yes, there are differences. I know they very well could be totally unrelated, and viruses be totally uninvolved. But I'm sure there could be ways of explaining the differences as well under this hypothesis. For example, maybe it's because during acute infection, everything is very uncontrolled. The virus enters through some random route with a variable initial viral load, and the body has very little "memory" of this pathogen. In contrast, in ME/CFS, maybe the virus is kept in a little highly controlled zone in a tissue, and the method and degree of "escape" or proliferation of the virus is very consistent after exercise. The adaptive immune system is constantly seeing it, so it can respond very predictably every time.

(Edit: I think I misunderstood what you were saying here and answered about the delay always taking the same amount of time in ME/CFS and not in acute infection. But in terms of symptoms flipping on like a light switch after a delay, see the next text and the edit added at the end.)

You already saw me say this, but for anyone else, I previously found two anecdotes of a symptoms "flipping on" like a light switch some time after a COVID infection, kind of like how some describe PEM. Yes, it's only two people, but still may point to more of a connection between the conditions.

Not instant, but this person on Reddit says after testing positive for COVID 1.5 days earlier, they went from a little sleepy to very sick in one hour, though no mention of fatigue as one of the after symptoms.

This person got intense fatigue and fever within an hour, after three days of muscle aches.

---

In any event, you should be able to test that hypothesis by checking the viral load before/after exercise. But then, the test is unlikely turn up anything if the patient was negative for virus to begin with.

Yeah, that's one thing I'm hoping for, but if viruses are involved, it will require technology to detect them in the first place. It seems like they're gradually getting better at detecting the COVID virus persisting, so maybe eventually they'll test viral levels before and after exercise in long COVID ME/CFS, probably long before something similar is done in pre-COVID ME/CFS.

---

Edit: I will say, for those whose symptoms just "switch on" after some time, it is harder to compare that to the gradual increase of viral load. I may be biased by my own symptoms, where it feels like a very gradual increase in symptoms over a couple days. I don't know exactly how or if a sudden symptom increase could be explained by viruses.

Maybe something like at first after exercise the virus increases in a "safe zone" of a tissue where it doesn't cause symptoms. But the moment it reaches levels where it escapes, one or two days later, maybe into the blood stream, the symptoms start.

But I agree it makes the hypothesis harder.

 

[forestglip]

Hargreaves analyzed 30 cases of poliomyelitis and confirmed the previous findings by Russell that physical exercise in the preparalytic phase was associated with grave prognoses. Furthermore, he suggested that severe mental stress such as driving a car over long distances, appeared to be equally disastrous.

I looked at the study to see what it says about this "mental stress" and it's just two people (participants 34 and 38) that took >250 mile drives during the preparalytic stage of polio. It's not totally clear, but it looks like one died, and it doesn't give details about the other. I think maybe he wrote the wrong participant number, because there is no data for No. 34 in the table. I don't think much can be concluded from this about mental stress.

But here's the main data for the physical activity causing worse outcomes:


Here are the degrees of physical activity:

Nil = in bed.
1 = not more than 1/4 (1/2 maybe?) day light work (e.g. resting in house, with short walks).
2 = Average light work (e.g., secretarial, housework, school).
3 = Average or heavy manual work (e.g., factory, labourer, athletic sports).

All 5 that had a day during the preparalytic stage doing level 3 activity died. Out of the 10 that did bed rest every day, 6 had no paralysis, and all 10 survived.

 

[Wyva]

You can put a flu/cold patients on 2-day CPET test and see if the performance decreases on the second day. No reason why you can't. It may need to be controlled for the worsening of infection on the second day though. Perhaps you can do that by comparing the viral load, etc. People who are sick with typical flu/cold should do fine with 10-100W in 10 minutes, I'd think.

Or, you can ask Michael Jordan. He once played full 60 minutes during a championship game with flu.
In my personal experience, moderate exercise during flu/cold, when I can muster, does not make the symptoms worse the next day.

I was very athletic before my ME/CFS onset. I did strenuous workouts regularly, HIIT and strength training mostly. These were really hard workouts, not for untrained or moderately trained people. Since this was a lifestyle for me, whenever I caught a cold, I kept doing my workouts like nothing happened. Colds are not so bad (not bad enough to stop you from working out) and I never noticed any PEM-like experience after my workouts. Maybe some mild discomfort during the workout due to the cold symptoms but not afterwards.

I never tried to do a workout with influenza, influenza is just too horrible with the very high fever. Even purely existing feels terrible. Getting off the couch is a challenge.

I tried to work out with mono/glandular fever, which triggered my ME/CFS, but gave up quickly as I felt way too ill to begin with. I don't remember any PEM-like experience during the infection but again, I felt really ill to begin with.