Researchers at BHC, the University of Utah and Columbia University teamed up to publish our most recent paper, Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. (1)

The purpose of the paper is to show that orthostatic stress (i.e. standing in place) leads to abnormal, measurable changes in circulation that cause illness symptoms and negatively impact function in many people with ME/CFS and Long COVID.

This abnormal circulation triggers symptoms like fatigue or weakness, brain fog, achiness, palpitations, cold hands and feet, nausea, exercise intolerance and even PEM. The general term that describes this phenomenon is orthostatic intolerance (OI), which simply means that illness symptoms develop while upright, and tend to resolve or improve when lying down. We have been trying to find easy ways to measure OI so that medical providers can recognize and treat it. We are also trying to understand the nature of OI in ME/CFS, because most people with ME/CFS have OI, yet only a portion meet the strict criteria for POTS* or several other defined disorders of OI. In fact, like many other aspects of ME/CFS, the nature and severity of OI seems to wax and wane, worsen in PEM or with illness severity, and change over time, even if illness limitations stay the same. It is our hypothesis that all types of OI are less well tolerated in ME/CFS due to unique deficiencies of cellular energy production. Muscle, gut and brain cells need a vigorous blood supply, but that is especially true if they are impaired to begin with!

In our first paper about OI, published in 2020, we showed that OI can be easily assessed in a clinic setting simply by asking about it. (2) People with ME/CFS have very abnormal scores on a standardized, validated OI questionnaire** compared to scores of healthy controls (P<0.001). There were similar findings on reported Hours of Upright Activity (HUA), defined as time spent with feet on the floor (seated, standing, walking) (P<0.001). Unfortunately, many clinicians want OBJECTIVE evidence rather than just listening to what patients report [even if it’s pretty obvious].

So in our second paper about OI, we set out to show that a simple bedside test can be used to objectively assess OI. (3) We administered the 10-Minute NASA Lean Test (a passive lean test) to 150 ME/CFS subjects (75 sick less than 4 years and 75 sick more than 10 years) and 75 healthy controls (HC). To our surprise, while very symptomatic, the ME/CFS patients with longstanding illness (as a group) could not be easily distinguished from HC based only on blood pressure or heart rate changes meeting established criteria during the lean test. This is consistent with published ME/CFS research showing that brain blood flow decreases during upright posture even when blood pressure and heart rate aren’t severely out of range.

There were supportive trends in our study, but only the ME/CFS who had been ill less than 4 years stood out compared to HC, and it was a unique measure that was the most statistically significant. This was the ratio of pulse pressure (PP) to systolic blood pressure (SBP), or PP/SBP. It sounds complicated, but the PP, which is simply the difference between the top and bottom number of blood pressure, should not be less than 25% of the SBP. If so, it suggests that there is a severe abnormality of circulation, not unlike septic or cardiogenic shock, and that the blood might not be getting delivered vigorously to all the places where it is needed. Remember, this is just while standing still in an upright position for 10 minutes. Just hearing this might make you want to lie down and put your feet up for a few minutes!

This brings us to the most recent paper. We enrolled 42 very ill people with Long COVID, 26 with ME/CFS and 20 HC in a study. They completed the 10-Minute NASA Lean Test, plus cognitive testing before and after. This simple, in-clinic, orthostatic challenge showed abnormally low PP/SBP values in Long COVID patients (most sick less than 2 years), even more strikingly abnormal than our previous study showing this finding in ME/CFS (sick less than 4 years). Meanwhile, both Long COVID and ME/CFS groups showed more negative impact of orthostatic stress on cognition than did the HC group. 

So why is BHC pushing the clinical education agenda about measuring orthostatic intolerance? Why, as one person asked me, have we “pulled the [10-Min NASA] Lean Test from the dustbin of history” when high-tech options such as Tilt Table Testing (TTT) exist? One reason is that TTT is not available to everyone, and OI is an important presenting aspect of ME/CFS and Long COVID, along with other post-viral syndromes. The NASA Lean Test can be cost-effectively done in a primary care clinic and carried out by trained nurses, physician assistants, or other supervised clinical staff, whereas TTT can only be done by specialists using special equipment. We must empower patients and their primary care providers to identify OI, which responds to treatment support, while the science moves forward to understand the physiologic underpinnings.

*POTS= postural orthostatic tachycardia syndrome
**The Orthostatic Hypotension Questionnaire (which we slightly revised as the Orthostatic Intolerance Questionnaire)

1) Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. (June 2022 full paper)

2) Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS. (August 2019 abstract only)

3) Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients. (August 2020 full paper)

10-Minute NASA Lean Test Information

Clinician Instructions

Patient Instructions

Orthostatic Intolerance: Symptoms, Diagnosis, Interventions

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