More than two years after the global COVID-19 pandemic, it is clear that infection with severe acute respiratory syndrome coronavirus 2 (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 impairments. 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 post-COVID syndrome.
Most patients with post-COVID syndrome 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 addition, in some patients with post-COVID syndrome, chest computed tomography (CT) scans revealed fibrotic lung abnormalities that may be partially responsible for their respiratory symptoms.
Hyperpolarized 129Xe MRI pulmonary measurements are driven by the unique properties of inhaled 129Xe gas, which in the healthy human lungs 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 lungs.
HP129Xe MRI scan provides regional information on pulmonary vasculature integrity. It enables 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 post-COVID syndrome. The participants also had chest CT scans, spirometry, a 1-minute sit-to-stand test, and measurement of hemoglobin level and Dyspnea-12 score.
Results
36 participants were enrolled, 11 patients diagnosed with post-COVID syndrome syndrome who had never been hospitalized, 12 patients with post-COVID syndrome who had been hospitalized for acute COVID-19, and 13 healthy volunteers who had not been infected with SARS-CoV-2. The SARS-CoV-2 infection was confirmed by reverse transcription–polymerase chain reaction or positive anti-SARS-CoV-2 antibodies. Patients with post-COVID syndrome who had been hospitalized had no history of intubation. None of the nonhospitalized post-COVID patients had evidence of previous pneumonia, but the authors mentioned the possibility that all of them were not imaged during their acute infection. Participants with post-COVID syndrome 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, had 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. There were no significant differences in spirometry measurements between the two subgroups.
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 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 non-hospitalized 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. 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 decrease diffusing capacity.
Picture from the original article of Grist et al.
Conclusion
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 post-COVID syndrome. 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 post-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) https://doi.org/10.1148/radiol.220069
