Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with ME/CFS, 2021, Rowe et al

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract
Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls.

Materials and Methods:
We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress.

Results:
There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response.

Conclusions:
The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

https://www.mdpi.com/1648-9144/58/1/28

 

Thank you Drs Van Campen, Rowe and Visser. That needed to be done and you did it. Merry Christmas.

 

Does this tell us anything more than that people who are positive on a tilt test are positive on a tilt test? There do not seem to be any denominators anywhere.

 

Reductions in cerebral blood flow and cardiac index.

 

Good to answer to the BPS argument that OI is caused by deconditiong, by noting LC participants were highly active before LC.

That's what many pwME have been saying for decades about our own disease.

Thank you very much to these researchers.

 

Which is presumably what a positive tilt test is about. But as far as I can see the paper simply shows that people that have this positive test have what you expect from a positive test. It would presumably show the same if you took people without either ME or Long Covid who happened to have a positive tilt test.

 

Yes - - they also mention "early-onset orthostatic intolerance symptoms" which is another challenge to the deconditioning hypothesis, i.e. patients developing OI before they've had time to become deconditioned.

 

I have difficulty understanding your logic. Yes presumably those who have found to have a positive tilt test so far, from the same team's previous publications, have been known to have decreased blood flow on doppler and decreased cardiac index. The novel idea (and i have to say, i have not yet read the paper) is that patients with Long-Covid have this feature too, seemingly.

To me, it signifies that there are hemodynamics similarities between Long-Covid and ME suggesting similar pathologies. POTs is highly disabling and poorly understood and in fact in my area there is a doctor that simply says that POTS is a Central Sensitization Syndrome feature (for which i disagree).
POTS prevalence and causes deserve to be researched and formally assessed in patients with both ME and Long-COVId because there are treatments for that and because it causes much disability.

I am thankful for the work of Van Campen et al because they lay out for all doctors and researchers that there are similarities with both diseases and that it can be measured. It represents a shout out to not disregard ME research and for other researchers to enter the field and understand why. Hopefully there is a remedy to whatever is the problem.

 

I think it is necessary to be clear as to what we mean by BPSers in this context. I don't think this was the creation of those usually thought of as the early BPSers. I think it was a dogma which they inherited and were no doubt taught. Their failure to test it was certainly an egregious error. However there must presumably have been a departmental view on this matter. Even if The Engel paper is taken as the origin of the BPS approach there was still 10 years development of the ideas before SW et al appeared on the scene.

 

I'm unclear as to how the COVID patients were selected or that selection bias has been avoided. By definition those attending the Stichting CardioZorg clinic will have had suspected ME/CFS or suspected Cardiac features, so we are not talking about a random sample of age/gender matched COVID patients, but age/gender matched COVID patients with suspected ME/CFS or cardiac problems. In which case what is the comparison aspect of this study telling us ?

Concern regarding the lack of random selection might be elevated given that three out of ten COVID patients had hypermobility which is perhaps surprisingly high. This symptom was then control matched.

Possibly not of significance but the age range across the study was quite young, average 30 +/-7 years.

Regarding the deconditioning question, I don't think this study adds anything. The pre illness status of the COVID patients doesn't matter because by definition they have already been ill for some time ( 1 - 1.8 years) and the arguments around deconditioning are predicated on days/weeks of inactivity rather than months.

Maybe there is something valuable in this study but I can't see that it says much beyond "we found A = A" .

Stichting CardioZorg https://stichtingcardiozorg.nl/

Prevalence of generalized joint hypermobility, musculoskeletal injuries, and chronic musculoskeletal pain among American university students - Discussion section on epidemiology

https://peerj.com/articles/7625/

 

Not directly related but I remain totally confused at how this "deconditioning" argument even continues to be entertained while millions of people live relatively healthy lives, certainly not suffering any of those symptoms, despite being completely sedentary. There are millions of people who have severe physical disabilities, sometimes keeping them completely paralyzed, and they do not suffer those symptoms.

Stephen Hawking did not exercise for his entire adult life. Still a damn genius, no brain fog there.

It's completely farcical in the face of so much conflicting evidence, it's seriously a complete rejection of common sense. How does something so obviously wrong continue to be a default explanation that has to be proven wrong even though it never had to be proven right? We can't make progress when nonsense turns reality on its head.

 

Basically what CRG says above.

 

Noticed you posting & wondering how are you feeling @Jonathan Edwards ? ... been thinking about you after reading omicron on another thread hope you ok?

 

Thank you @CRG and @Jonathan Edwards. It is a case of early attrition-those presenting or being referred to that mecfs cardiac clinic are already categorized as hemodynamically challenged. The consecutive patient choice is therefore not providing reassurance.

In terms of making this research methodology stronger, what recruitment methods would make it stronger, keeping in mind that the case definition for Long Covid may still be blurry ?

Edit to add: the authors acknowledge the recruitment problems:

 

Seem to be getting over it quickly. Not so much Covid as Jabvid - the feeble sort you get after everyone has been jabbed.

 

Isn’t that the name of the Health Secretary? Haha

 

V.long reply posted here https://www.s4me.info/threads/deconditioning-–-relevance-and-irrelevance.24028/ as too off topic for this thread. One point of note is that in “Deconditioning does not explain orthostatic intolerance in ME/CFS"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525293/

van Campen et al classify deconditioning in terms of CPET response as:

%peak VO2 ≥ 85% = no deconditioning,

%peak VO2 65–85% = mild deconditioning,

%peak VO2 < 65% = severe deconditioning

which creates a circularity <85% peak VO2 = deconditioning and deconditioning = <85% peak VO2, I'm not clear what that means for the study being discussed in this thread but my sense is that it creates a double circularity something like B=A=A=B ???

 

The methodological problems go deeper than mere recruitment, it’s not clear at all what the authors are seeking to do.

There is no stated study hypothesis, rather there is a sort of statement of intent:

“To investigate the overlap …[of] … clinical phenotypes."

Phenotypes being defined by symptoms and hemodynamic findings during orthostatic stress symptoms in long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. The problem with this construction is that overlap is presumed rather than questioned. As the authors put it:

“Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome”.

Just because a phenomenon has been reported elsewhere doesn’t mean that:
a) it is real or
b) that it should be expected to be found in a given research project. This assumption can be a major source of bias – you find what you expect to find.

There is a second statement of intent further into the paper:

"To further explore whether the similarity in chronic symptoms of patients after SARS-CoV-2 infection (long-haul COVID-19) and ME/CFS extends to objective hemodynamic abnormalities, …….."

The establishment of “similarity” relies on a number of references, it’s not clear why the authors are doing this or how this serves meeting the earlier stated intention of comparing phenotypes – is the intention to compare or is it to identify similarities ? and to what end ?

Unsurprisingly similarities are found, supported by favourable references. And conclusions are reached reliant on assumptions not tested by the research e.g:

“ The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning.”

Of note is that the authors are:

a) relying on patient report for the onset of symptoms, - testing did not take (in 9/10 subjects) till 6 months plus after Covid infection.
b) referencing cardiovascular deconditioning despite not measuring this or any other deconditioning aspect within the study.
c) discounting short term (ie 7 -21 days deconditioning as a possible vector for the development of POTS, without explanation.

This is all very frustrating because it seems possible that there is useful work be carried out by these authors, but they badly need the involvement of someone with strong methodological skills to ensure their work has validity.

 

A key part of an ME/CFS diagnosis is that symptoms are not due to other causes. In the case of long covid, other causes seem very possible - regardless of matching ME/CFS symptoms.

Many people in the ME/CFS field believe that some long covid is indeed ME/CFS, but that most cases are not. If we look at the representative ONS UK household survey (regularly testing people for Covid and following up on long-term symptoms for over 100,000 people), over 40% have loss of smell or taste, 39% have problems breathing and these are not ME/CFS symptoms. And only 31% have problems concentrating — something that most patient surveys find is a problem for over 80% of patients.

As @CRG has pointed out, the patients in this study are likely to be a biased sample.