Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and ME/CFS, 2022, Vernon et al

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

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I cannot figure out what is supposed to be shown in Figure 1. Seems like symptom severity increases for healthy controls according to the top charts, but then the percent change is negative in the bottom charts.

 

From the Background in this article:

"Common laboratory tests are often unrevealing."

Absolutely true.

" I can't find anything wrong." Tragic, really to be told this over and over again. Many with this terribly debilitating disease have heard this phrase that dead ends investigations into the disease that has upended their lives. And, so completely frustrating to know one's physical functioning has gone very wrong, but not be able to convince one's family physician of this.

It's good to see this study. Simple in office assessments can indeed reveal OI.

@LarsSG thank you for posting this article. Sorry I can't help with the charts in your post above.

 

The tables are a mystery. Seem to completely contradict the text. An error somewhere?

Interesting that the HR for the HC went up so much, too, close to POTS levels on average (table 2). The increase seems too much to be driven by the 5 POTS cases in that group?

Another unusual finding was a rise in diastolic BP with stable systolic BP. They point to one other study that found the same:
https://www.s4me.info/threads/ortho...milarities-with-me-cfs-2021-rowe-et-al.23979/

This seems to be the cognitive testing app they used: http://www.danabrainvital.com/

 

The paper says the unusual thing is that the low pulse pressure comes from a rise in DBP. Apparently in other conditions it is caused by a drop in SBP.

 

And mine—in relation to the systolic pressure, at least. 107/89 would be the sort of range for a bad day.

It's not like that all the time, though. I was recently asked to record BP, resting heart rate, and single-lead ECGs twice daily for two weeks, because as well as low pulse pressure, I keep getting intermittent high blood pressure, resting heart rate in the low 40s, and AF alerts and symptoms.

The average BP reading was 118/82, average resting heart rate was 51, and although I got numerous AF warnings during the period and recorded a symptomatic episode on ECG, I never captured one at the scheduled morning/evening recording.

I've no idea what triggers the weird episodes, but on paper I'm in perfectly good shape for someone in their 60s.

 

My diastolic pressure is fairly consistently higher than it should be. Systolic is pretty good.

I had a supine vs. standing HR test with exactly the same values for both positions.

About 30 to 45 minutes after a treadmill test I almost fainted. Unfortunately this was after I left the test, and was therefore not noted by medical practitioners who didn't believe any of my reports of illness.

 

It seems like the 30bpm POTS threshold is kind of arbitrary and ME patients often seem to end up just above or below it. About 25bpm on average seems normal for controls.

 

Dr Klimas used to ask her patients to do a home test for 7 days in a row. In my case, I met the case definition for POTS for 3-4 days and on 2 days I needed to stop the test because of near fainting events. The tilt table test, a true one, amplifies the abnormal autonomic response and if someone would only have 25 bpm increase on a Nasa lean, then they are likely to meet the threshold on the tilt table

Regardless, it has been demonstrated by Rowe et al that nearly all patients with ME have reduced blood flow regardless of the POTS status.

 

I also find that being horizontal is pretty important for me in being able to do things, but I'm not convinced it has anything to do with blood pressure or heart rate in particular (just wildly theorizing, it seems to me that these changes might be secondary to whatever is actually the problem). FWIW, my lean test results are just under 30bpm and just under 25% PP/SBP (mostly rising diastolic as in this study), but that's only a little worse than the average for the healthy controls in this and their previous study, so it's not really clear to me that it is meaningful.

I really wish we had some solid data on cerebral blood flow, ideally supine, seated and standing.

The average for healthy controls in this study was 27bpm and 24bpm in their previous study, so if 25bpm on a lean test is enough to meet the POTS threshold on a tilt table that would mean that about half of generally healthy people have POTS (or their control groups are particularly prone to POTS).

 

Agreed. Your data is incredibly varied and points to issues with these studies and the use of the lean test in a clinical setting. It would be interesting to see a study that had participants do a short lean test daily for a couple weeks to see if the kind of variability you have is common in ME patients and how much variability is normal in healthy controls. Seems like this would be possible now with a wearable device. Maybe you'd find a correlation between ME symptoms and OI and/or POTS symptoms.

Their earlier study found a difference between ME patients less than 4 years after onset and ME patients more than 10 years after onset. And this recent study found not much difference between HC and ME in blood pressure measures, but quite a bit difference between HC and LC (specifically, LC had a big rise in diastolic BP). So maybe that's related, as the LC patients would have all had quite recent onset. But if POTS and OI improve over time without overall symptoms improving in ME does that mean POTS and OI aren't causing other symptoms?

I think congestive heart failure, aortic valve stenosis and cardiac tamponade are all unrelated because those would be associated with lower systolic BP, but what we're looking at is raised diastolic BP (they point out in the study that this lowered PP is usually because of lowered systolic, not raised diastolic).

In any case, it really seems like you'd need a lot more data to draw any kind of firm conclusions on this. The big question for me is if this is causing other symptoms, just a symptom itself or even some form of compensation for another problem. It seems like some ME patients are helped by POTS and OI treatments.

 

I had a pulse pressure of 20 at times. I interpreted it as likely being due to low blood volume (mimicking the effects of major blood loss). It varied a lot over time so seems to make heart disease as cause of it unlikely. Faulty regulation of blood volume and water content of the body seemed to fit.

This kind of dysregulation could be due to blood pooling in the lower body (including belly) which would result in the kidneys perceiving there to be an excess of fluid, and setting their target fluid volume lower. Whole body blood volume would be reduced, with stress on the heart and poor cerebral blood flow.

The blood pooling could be due to a failure of proper vasoconstriction due to nerve damage, or excessive laxity of tissue.