Autonomic phenotyping, brain blood flow control, and cognitive-motor-integration in Long COVID and [ME/CFS]: A pilot study, 2025, Edgell et al

[Nightsong]

Abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the prolonged sequelae after COVID-19 (>3 months; Long COVID) have similar symptomology, are both associated with autonomic dysfunction, and a growing proportion of Long COVID patients are developing ME/CFS. We aimed to determine an autonomic phenotype of patients with ME/CFS vs Long COVID. We hypothesized that the groups would differ from controls yet be similar to one another. We recruited sedentary controls (n = 10), mild/moderate ME/CFS patients (n = 12), and Long COVID patients (n = 9) to undergo 1) breathing 5 % CO2, 2) breathing 10 % O2, and 3) 5-minutes of 70° head-up tilt. Respiratory, hemodynamic, and cerebrovascular variables were measured throughout the 3 trials. Resting vascular function and cognitive-motor-integration were also assessed. ME/CFS and Long COVID were similar to the healthy controls and each other with regard to resting vascular function and the hemodynamic responses to hypoxia, hypercapnia, and head-up tilt (p > 0.05). However, in ME/CFS we observed a greater reduction of cerebrovascular resistance (p = 0.041) and impaired autoregulation (p = 0.042) during hypercapnia alongside impaired cognitive-motor integration (p < 0.02), and in Long COVID we observed reduced peripheral and end-tidal oxygen (p < 0.04) and less vagal withdrawal during tilt (p = 0.028). Our findings suggest unique phenotypes when comparing ME/CFS and Long COVID whereby we have shown that Long COVID patients experience hypoxia while upright contributing to less vagal withdrawal, and ME/CFS patients experience impaired cerebrovascular control during hypercapnia potentially leading to reduced cognitive-motor integration. These differences could stem from disease severity/duration or some unique aspect of the COVID-19 virus.

Link | PDF (Autonomic Neuroscience, October 2025, open access)

 

[Mij]

HIghlights:

ME/CFS and Long COVID patients have autonomic and cognitive impairment.
•
ME/CFS patients have a greater reduction of cerebrovascular resistance during hypercapnia.
•
ME/CFS patients have reduced cognitive-motor-integration at rest.
•
Long COVID patients have a greater reduction of peripheral and end-tidal oxygen during upright tilt.
•
Long COVID patients have less vagal withdrawal during upright tilt.

 

[DHagen]

I am almost always confused by what, at times, appear to be arbitrary and inconsistent methods of differentiating between "Long Covid" and ME/CFS .

Here, regarding the differentiation between those subjects with ME/CFS and those with "Long-Covid," the paper states (p. 7):

Patients clinically diagnosed
with ME/CFS who described their symptoms as mild to moderate (self-report) and with no
history of contracting COVID-19 (self-report) were recruited (n =12). All patients were able to
come to the lab independently for testing with minimal aid. Patients experiencing post-acute
sequelae of COVID-19 (Long COVID) for >3 months after infection with COVID-19, diagnosed
by i) positive RT-PCR, ii) positive rapid antigen test, or iii) a licenced physician, with no prior
history of chronic fatigue were recruited in the Long COVID group (n=9).

Fair enough, so it seems, essentially, that if they developed their symptoms following COVID-19, they were placed in that cohort. Fine.

But the paper also cites Tokumasu's 2022 study in stating (p. 4):

a recent study has found that 17% of a cohort of Long COVID
patients subsequently developed ME/CFS

Tokumasu et al class long-covid simply as "symptoms that persist for more than one month after the onset of COVID-19," while for the ME/CFS patients:

we used three internationally standardized sets of ME/CSF criteria for the eligible patients: the Fukuda criteria [9], the Canadian Consensus Criteria (CCC) [10], and the IOM criteria [11]. Between late April and mid-May 2022, the co-authors shared the task of reviewing all patient medical record data to check whether patients met each of the three criteria for ME/CFS. As a reconfirmation, the principal researcher and outpatient physicians who managed the patients reviewed the medical record data for patients who met each of the three criteria for ME/CFS. This process was used to establish the ME/CFS group.

So it doesn't seem that Edgell et al are using the same standard, that is, they are not classing patients' condition as ME/CFS based upon severity, as Tokumasu et al appear to do, but rather draw a hard line based upon COVID-19 infection prior to the development of symptoms, regardless of severity.

Unless I have misunderstood or simply missed something altogether, of course.

 

[EndME]

HIghlights:

ME/CFS and Long COVID patients have autonomic and cognitive impairment.
•
ME/CFS patients have a greater reduction of cerebrovascular resistance during hypercapnia.
•
ME/CFS patients have reduced cognitive-motor-integration at rest.
•
Long COVID patients have a greater reduction of peripheral and end-tidal oxygen during upright tilt.
•
Long COVID patients have less vagal withdrawal during upright tilt.

A key result also seems to be no difference in POT(s) between patients and controls if the abstract is to be believed.

 

[SNT Gatchaman]

There were no differences in the responses to HUT between groups regarding the 30:15 ratio, maximal change in HR, change in SBP or DBP within 30 seconds, and change in systolic or diastolic blood MCAv with 30 seconds of tilt (all p≥0.051, Table 4). From these data, it is interesting to note that while no participant was previously clinically diagnosed with a condition of orthostatic intolerance, we observed an increase of HR to >120bpm in 5 HC, 3 ME/CFS, and 4 Long COVID patients during HUT meeting a diagnostic criteria for POTS. Additionally, we observed a fall of systolic blood pressure of >40mmHg or a fall of diastolic blood pressure of >20mmHg within 15 seconds of tilt in 1 HC and 1 Long COVID patient meeting the criteria for initial orthostatic hypotension.

 

[Eddie]

A increase of HR to > 120bpm isn't the criteria for POTS. There is a graph that shows two people would qualify for POTS with changes in heart rate of around 45 and 35 in the ME group. There are 3 controls who had heart rate increases around or just below 30. None of the Long Covid patients had heart rate increases above 25.