New MRI technique reveals the oxygen from the lungs is having trouble getting through to the small blood vessels in long COVID. It could explain shortness of breath and exercise problems in long COVID and possibly ME/CFS.

The Breathing-Oxygen series continues on Health Rising with an intriguing new long-COVID study that could have ramifications for chronic fatigue syndrome (ME/CFS) as well.

Health Rising recently produced a review of an exercise study that found that “gas-exchange” problems were preventing people with ME/CFS from producing normal amounts of energy during exercise. The study found alterations in ventilation during exercise which suggested that people with ME/CFS may be breathing more deeply and slowly in an attempt to shove more oxygen from their lungs into the blood.

This new Canadian long-COVID study found problems with “gas exchange” as well – but this time on the cellular level.

Lung function tests are usually normal in long COVID, but many people experience shortness of breath and exercise intolerance. This study may have revealed a cause.

Many people with long COVID experiencing shortness of breath, fatigue, dizziness, and other symptoms are being met with normal lung function test results. In the past, a result like that would have led researchers to conclude their symptoms are psychological in nature and to ignore them. Many doctors now are probably telling their long-COVID patients that their lungs are fine and they should go home and exercise.

We can dig deeper now, though – and that makes all the difference. On the ME/CFS side, we’ve always thought that new technology would make the difference – the problem has been getting to it. The low funding and interest in the ME/CFS field means it takes longer to get access to the new technologies that can really dig deep.

But then came long COVID – a virtual stand-in for ME/CFS –  which does have funding – and here we have a small Canadian study (n=40) from the LIVEFREECOVID project which used a new imaging technique to dig much deeper into the “gas-exchange” issue than has ever been done in ME/CFS.

A CT study of hospitalized patients provided one clue, though: microclots and/or blood vessel changes were causing the blood to be shunted away from the smaller blood vessels, where the majority of gas exchange takes place, to the larger blood vessels. Another study found evidence of small airways disease in long-COVID patients whether they’d been hospitalized or not.

The Technique

That led a Canadian group to try what is apparently a fairly new imaging technique that employs radiolabeled xenon gas to assess the functioning of the tiniest blood vessels in the lungs. Two years ago, Grace Parraga, one of the co-authors of this study, lauded the new technique, stating:

“Xe MRI provides rapid, sensitive, non-invasive, and simultaneous measurements of pulmonary ventilation, lung tissue microstructure as well as diffusion within the alveolus and into the alveolar tissue and red blood cells, providing new opportunities to more deeply investigate lung diseases and unravel enigmas in respiratory medicine.”

This technique enables researchers to actually watch the oxygen moving through the membrane of the lung cells into the blood. The microvascular blood vessels and the microcirculation in general, are, of course, of great interest in ME/CFS and fibromyalgia (FM) as well. This study also used CT scans.

The Study

The study “Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndromefindings were stark.

The CT scans found that many of the very smallest blood vessels – the ones that allow the oxygen from the lungs to diffuse into blood – were simply gone in previously hospitalized in long -COVID patients. This was not true in people with long COVID who had not been hospitalized.

They did, however, find problems with oxygen diffusion into the small blood vessels even in people with long COVID who had not been hospitalized. The Canadian study was quickly followed by a small Oxford xenon study, “Lung Abnormalities Depicted with Hyperpolarized Xenon MRI in Patients with Long COVID“, which produced similar results.

In an editorial “Step on the 129 Xe Gas: The MRI Race to Uncover Drivers of Post-COVID-19 Symptoms” published alongside the Oxford study, Parraga and Matheson (two co-authors of the Canadian study) emphasized how important the findings were for the vast majority of long-COVID patients who experienced an initial mild illness and were never hospitalized.

“…the take-home message is clear: you don’t need to have been hospitalized with a severe COVID-19 infection to suffer long-term symptoms and abnormal MRI gas-exchange measurements. Moreover, even if spirometry, DLco, and chest CT are normal, symptoms and 129Xe MRI gas-exchange abnormalities persist for long periods of time post-infection.”

These findings seem to jive with a recent long-COVID study – produced by ME/CFS researchers, by the way – which found bizarre breathing patterns during exercise in almost 90% of long-COVID patients.

Uneasy Breaths: Strange Breathing Patterns in Long COVID May Contribute to Exercise Intolerance


The Canadian study author’s first guess as to the cause involved microclots blocking oxygen from freely flowing into the capillaries. Other possibilities included damage to the blood vessels, the blood being shunted past the small blood vessels, and “vascular remodeling” which can produce narrowed blood vessels.

The Gist

  • Despite the shortness of breath and problems exercising, lung functioning studies are usually normal in long COVID. In the past, a finding like that has led the medical profession to go down the psychological rabbit hole.
  • Technology has improved, however. Two studies employing a new MRI imaging technique that’s able to measure the gas exchange between the lung cells and smallest blood vessels may have found an answer.
  • Even in the long-COVID patients who had not been hospitalized, the Canadian and Oxford studies both found reduced rates of oxygen diffusion from the lungs into the small blood vessels where gas exchange occurred.
  • Many small blood vessels appeared to have been pruned away entirely in formerly hospitalized long-COVID patients.
  • The problems long-COVID patients have moving oxygen into the small blood vessels exercises may mirror what we recently saw in ME/CFS. People with ME/CFS have developed a strange breathing pattern apparently in order to shove more oxygen into their lungs, and ultimately, their blood as well.
  • A recent blog reviewed a long-COVID study – produced by ME/CFS researchers – which found that bizarre breathing patterns appeared during exercise as well.
  • The Canadian authors proposed four possible mechanisms for the poor gas exchange between the lungs and the blood. (Note that gas or oxygen = energy, so poor gas exchange equals poor energy production).
  • All four – a shunt that propels blood away from the lung cells, micro blood clots, narrowed blood vessels, and damaged blood vessels have all been hypothesized to happen in ME/CFS. The Ron Davis/Open Medicine Foundation findings of poorly deformable red blood cells could also contribute to problems with gas (e.g. energy) exchange.
  • The Canadian authors are continuing their studies.


The narrowed blood vessel idea was intriguing because narrowed blood vessels could help explain the low blood volume found in ME/CFS. Because blood volume is a function of blood vessel volume, abnormally narrowed blood vessels could result in reduced blood volume.

The central theme was “increased vascular resistance”; i.e. more difficulty getting the blood to flow through the blood vessels. Besides the shortness of breath sometimes seen in long COVID, they noted that their findings could also explain the exercise problems commonly found.

The leader of the million-dollar study, Grace Parraga, seemed confident they’d found a key problem in long COVID and was looking forward to figuring out exactly why this is happening.

“Now that we have the what’s happening, where it’s happening and when it’s happening, we can figure out the why and the who,”

A one-year follow-up study is underway.

Two Gas Exchange Diseases? The ME/CFS / Long-COVID Connection

You might say – well, since COVID-19 often affects the lungs – you might expect there would be lung problems in long COVID – but what about ME/CFS? It’s never been associated with lung problems. No one has ever dreamed of doing a xenon gas study in a disease like ME/CFS, which has never been thought to be respiratory in nature.

The authors of the Canadian study noted, though, that they didn’t find lung or respiratory problems in long COVID – they found vascular or blood vessel problems. To this layman, at least, that suggests their findings could potentially apply wherever the small blood vessels are found.

One of the main avenues of attack by the coronavirus, after all, is the endothelial cells lining the blood vessels. All four of the possible causes put forth by the Canadian researchers to explain the gas exchange problems they found in long COVID have been proposed at one time or the other in ME/CFS. They include microclots, damaged blood vessels, a shunt, and “vascular remodeling”, which produces narrowed blood vessels.

Clotting was, for a short time, a pretty hot topic in ME/CFS and could result from damaged endothelial cells. Systrom has suggested that small nerve fiber damage could be shunting blood away from the muscles in ME/CFS. Wirth and Scheibenbogen proposed that narrowed blood vessels in ME/CFS are triggering an explosion of vasodilators which, in turn, are producing a wide array of symptoms. Those narrowed blood vessels could be reducing blood volumes. (I haven’t found a blood volume long-COVID study yet.)

Damaged Small Nerve Fibers May be Causing Energy Problems in Chronic Fatigue Syndrome (ME/CFS)

Hypothesis Predicts Major Failure Point in Chronic Fatigue Syndrome (ME/CFS)

Plus, we have our own ringer – the Ron Davis/Open Medicine Foundation work on red blood cell deformation – that could be impairing blood flows as well. As noted at the start of the blog, we also have an exercise study that suggests that people with ME/CFS are doing everything they can, breathing-wise, to shove more oxygen into their blood.

Any researchers up for an ME/CFS 129Xe MRI lung study?

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