Persistent Exertional Intolerance after COVID-19: Insights from Invasive Cardiopulmonary Exercise Testing, 2021, Singh, Systrom et al

Abstract

Background
Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies.

Research question
What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease?

Study Design and Methods
This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort.

Results
Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO2) compared to controls (70±11%predicted vs. 131±45%predicted; p<0.0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (i.e., narrow CaVO2/CaO2) compared to controls (0.49±0.1 vs. 0.78±0.1, p<0.0001) despite a preserved peak cardiac index (7.8±3.1 vs. 8.4±2.3 L/min, p>0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO2 slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation.

Interpretation
Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.

Open access, https://journal.chestnet.org/article/S0012-3692(21)03635-7/fulltext

 

Does this suggest distributed vascular damage? That would fit with Covid bloodclot issues.

 

One of the authors, in layman terms:

https://twitter.com/user/status/1425514991919276036


And Jennifer Brea has a thread of similar past research in ME and LC:

https://twitter.com/user/status/1425510540085014531

 

I was thinking more the deranged muscle vasodilation / vasoconstriction as per Wirth and Sheinbenbogen (2021), which could impair the peripheral VO2 limit.

Not sure how relevant/valid, but when I looked back at my estimated VO2max per Apple Watch 6, it looks like this. I got sick initially mid Dec-mid Jan.

 

Thank you - that's reassuring. My graph then likely reflects both my reduced activity and higher baseline heart rate (POTS). My resting heart rate has gone from a lifelong (though probably flattering) 48-52 to 65. If just standing now increases it to 100, even modest exercise is likely to be similarly higher than my year-ago normal.

No it doesn't offer them daily, only when working out. Working out could be a brisk walk, but that has been off the table for a couple of months now. I think the slope in my graph reflects the incremental reduction in my activities as my illness took effect in these initial months: first stopping going to the gym, then riding my bike only once a week, then not at all...

Probably the estimated VO2max from wearables is of limited value in this context. I imagine their benefit is more in showing an improvement with exercise in normal but unfit people. Those with some form of developing disease are probably going to recognise symptomatic limitations before the watch highlights it.

 

Any simple algorithm relying on heart rate is assuming normal heart rate regulation. In OI, either POTS or NMH, heart rate can be different, and so throw the algorithm off. I am much less sure about the new type of OI found in us. We still know almost nothing about it.

 

There was a report a year or two ago following a new type of brain scan. Our brain blood pressure can be lower than our peripheral blood pressure. I do not recall other details, and have only seen this once. It may be wrong, but it may explain why some of us seem fine on a tilt table test yet have all the symptoms.

 

Drops of 27% in 3 weeks can only occur in highly trained athletes, not people within a standard deviation of the mean.
It is important not to compare apples to oranges, a point which seems to have escaped those authors.
Note that reference 26 is a 1968 editorial which doesn't present primary data. Reference 25 demonstrated a 7% drop in two weeks in "healthy young men" which doesn't support the claim either.

 

These devices have no meaningful way of knowing much about a person's cardiovascular fitness anyway, as you've said many a time. They have some idea how much the wearer exercises, and limited information about their resting heart rate and response to activity, but that's all.

I think my 'excellent cardio fitness' – I'm apparently in the top 10% of women in my age group – is based entirely on my normal BMI, our family's tendency to bradycardia, and the fact that a wrist-worn device can't measure heart rate accurately in water and swimming is the only form of exercise I can do.

It's good at recording how many laps I've swum and how fast, which is useful because reduced swimming speed is a good sign that my energy levels are lower than I realised (I suspect technique drops off in quite subtle ways), but I mostly ignore the rest.

 

Was it one of these (my selection of interesting OI studies) @alex3619 ?

https://www.sciencedirect.com/science/article/pii/S2467981X20300044


https://www.frontiersin.org/articles/10.3389/fnins.2020.00688/full


(Unlikely to be this one. Very recent)
https://www.nature.com/articles/s41598-021-89834-9

 

Yes, this one:
Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography

 

This was a study that I was cheering about! It explained so much.

I have said (fairly repetitively) that I had horrendous symptoms during a tilt table test but nothing to speak about was recorded by the machines I was linked up to. I ended up being discharged with no further investigation.

My OI is much worse now, but I still haven’t plucked up the courage/energy to start all over again.

 

Moved from the long covid thread

New Haven Register: Long COVID fatigue may not be a heart or lung problem, Yale doctors say

"When cardiopulmonary tests don’t reveal a problem with the heart or lungs, “it’s not that they’re making things up,” said Dr. Inderjit Singh, a pulmonologist at Yale New Haven Hospital and lead author of a study about acute intolerance to exertion. It may be that the muscles are unable to extract oxygen from the blood. The study appears in the journal Chest.

"There are two main theories for the problem, Joseph said. One is that there may be “an abnormal connection between the arteries and the veins in the muscle bed. So oxygen is being delivered appropriately, but it’s bypassing the muscles and it’s not being absorbed by those muscles,” he said. Instead, oxygen is passing from arterial vessels directly to veins.The other possibility is “there’s some inflammatory hit to the mitochondria, which are the powerhouses of the cells,” and so they are unable to take up oxygen efficiently"

So far, there is no treatment for the condition, which also has appeared in patients with Lyme disease, chronic fatigue syndrome and other post-viral syndromes."

 

Merged thread
The study found out that LC patients have inability to extract oxygen in the peripheral tissues, for example, the muscles

A normal pulmonary exercise test consists of riding a stationary bicycle with a mouthpiece that measures oxygen consumption. In the invasive test, a catheter is placed down the right side of the neck into the heart and lung. Another catheter is placed in the wrist. Blood is drawn, “so we’re able to calculate the extraction of oxygen in the other tissues, for example, the muscle,” Singh said.

Normally, a patient should be able to extract 75 percent of the oxygen from their blood, but the long COVID patients are able to extract only 50 percent.

I saw several hypothesis that hypoxia is probably the issue in ME/CFS but I never saw that someone mesured it with an experiment like this. Could this be replicable also in ME/CFS? Is this a good method which could confirm that hypoxia is a problem in ME/CFS?

https://www.nhregister.com/news/art...p1NhoyNh-KZ1nmVsLI4XQZX2RJkxO8UBDzE3_kZ6zv-iA

 

This is related to David Systrom's earlier work (he's an author on the paper this article refers to). He's published other work using these investigations on ME/CFS patients, as well as Fibro and LC. There's also a related drug trial underway. We have discussed a few of these on here if you search