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Long COVID patients have abnormal gas exchange, measured by 129Xe MRI red blood cells-to–alveolar tissue barrier ratio

The authors from the United Kingdom and Germany conducted this pilot prospective study to evaluate hyperpolarized (HP) pulmonary xenon 129 (129Xe) magnetic resonance imaging (MRI) measurements of the pulmonary red blood cell (RBC)-to–alveolar tissue barrier ratio as a surrogate of abnormal gas exchange in a small group of nonhospitalized and posthospitalized patients diagnosed with long COVID syndrome. 

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than two years after the global COVID-19 pandemic, it is clear that infection with SARS-CoV-2 can lead to a new disease called long-COVID-19 or post-acute COVID-19 syndrome. Although over 200 symptoms have been reported, the most common are breathlessness, fatigue, and cognitive impairment (known as brain fog).

Symptomatic patients with long COVID typically have normal pulmonary function test results, and some of them have a normal or mildly abnormal diffusing capacity of the lung for carbon monoxide (DLCO). In some patients with long COVID, chest computed tomography (CT) scans revealed fibrotic lung abnormalities that may be partially responsible for respiratory symptoms.

Hyperpolarized 129Xe MRI pulmonary measurements are driven by the unique properties of inhaled 129Xe gas, which in the healthy human lung instantaneously fills the terminal bronchi and lung parenchyma, participates in transmembrane diffusion through the alveolar-capillary membrane, and binds to red blood cells (RBCs) in the pulmonary capillaries. This pulmonary functional imaging method provides a noninvasive way to simultaneously capture a subvoxel snapshot in time of inhaled gas delivery, flow, diffusion, and RBC binding throughout the entire lung.

HP129Xe MRI scan provides regional information on pulmonary vasculature integrity. It may enable the assessment of ventilation and gas transfer across the alveolar epithelium into RBCs even when CT scans and lung function test results are normal or nearly normal.

About the study

The authors investigated HP 129Xe MRI measurements of the pulmonary RBC-to–alveolar tissue barrier ratio as a surrogate of abnormal gas exchange in small groups of nonhospitalized and posthospitalized patients diagnosed with long COVID syndrome. The participants also underwent chest CT scans. The participants also had spirometry, measurement of hemoglobin level, Dyspnea-12 score, and a 1-minute sit-to-stand test.


36 participants were enrolled, 11 patients diagnosed with long COVID syndrome who had never been hospitalized, 12 patients with long COVID syndrome who had been hospitalized for acute COVID-19, and 13 healthy volunteers who had not been infected with SARS-CoV-2. Posthospitalized participants with long COVID syndrome had no history of intubation. Both groups of patients proved the SARS-CoV-2 infection by reverse transcription–polymerase chain reaction or positive anti-SARS-CoV-2 antibodies. Both groups of patients had no evidence of interstitial lung or airway disease or a history of smoking more than ten packs a year.

The mean time from infection with SARS-CoV-2 was 287 days ± 79 days for nonhospitalized participants and 143 days ± 72 days for posthospitalized participants.

Patients in both cohorts, nonhospitalized and posthospitalized, experienced breathlessness, with mean Dyspnea-12 scores of 9 ± 5 and 10 ± 5, respectively. The mean hemoglobin level for nonhospitalized and posthospitalized participants was 144 g/L ± 15 and 145 g/L ± 14, respectively. There was no evidence that oxygen saturations changed before or after the mBORG sit-to-stand test.

CT findings were normal or nearly normal. None of the nonhospitalized patients had evidence of previous pneumonia, but the authors mentioned the possibility that all nonhospitalized patients were not imaged during their acute infection. 

There were no significant differences in spirometry measurements between the two subgroups. The mean DLCO was normal, but significantly lower in nonhospitalized than in posthospitalized patients.

HP 129Xe MRI measurements of the pulmonary RBC-to–alveolar tissue barrier ratio

Both subgroups of nonhospitalized and posthospitalized patients had significantly lower 129Xe MRI RBC-to–alveolar tissue barrier ratio than healthy volunteers, indicating abnormal gas exchange. The measured abnormality on HP129Xe MRI scans appears to be only marginally greater in the posthospitalized participants than in the nonhospitalized participants, but there was no significant difference between the two subgroups.

DLCO, which measures pulmonary vascular integrity, was lower in the nonhospitalized group than in the posthospitalized group and correlated with the RBC-to–alveolar tissue barrier ratio. The authors stated that the nature of this abnormality needs further investigation. 

The authors emphasized that pathophysiological mechanisms that underlie the changes in HP129Xe MRI after COVID-19 remain unresolved. They said that a lower 129Xe MRI RBC-to-barrier ratio suggests that SARS-CoV-2 infection may have caused some microstructural abnormality to one or two volumes, such as pulmonary embolism, alterations in pulmonary blood flow, or a thickening of the alveolar membrane, leading to a decrease in blood volume. These factors are expected to cause a decrease in diffusing capacity.

Picture from the original article of Grist et al.


The use of hyperpolarized pulmonary xenon 129 MRI measurements of the pulmonary red blood cell-to–alveolar tissue barrier ratio showed an abnormal gas exchange in patients diagnosed with long COVID. Both, posthospitalized and nonhospitalized participants had lower 129Xe MRI RBC-to–alveolar tissue barrier ratios, suggesting abnormal oxygen and carbon dioxide gas exchange.

The authors concluded that underlying pathophysiological mechanisms behind long COVID symptoms remain poorly understood, making treatment decisions hard, if not impossible.

This article was published in Radiology.

Journal Reference

Grist JT et al. Lung Abnormalities Detected with Hyperpolarized 129Xe MRI in Patients with Long COVID. Radiology 2022; 305:709–717. (Open Access)



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