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Background SARS-CoV-2 targets angiotensin-converting enzyme 2 (ACE2) expressing cells in the respiratory tract. There are reports of breathlessness in patients many months post-infection. Purpose This study aimed to determine if hyperpolarized 129Xe MRI (XeMRI) imaging could identify the possible cause of breathlessness in patients three months after hospital discharge following COVID-19 infection. Materials and Methods This prospective study was undertaken between August and December 2020, with patients and healthy control volunteers enrolled. All patients underwent: lung function tests; ventilation and dissolved phase XeMRI, with the mean Red Blood Cell (RBC):Tissue Plasma (TP) ratio to be calculated; and a low dose chest CT scored for the degree of post-COVID-19 abnormalities. Healthy controls underwent XeMRI. The intraclass correlation coefficient was calculated for volunteer and patient scans, to assess repeatability. A Wilcoxon rank-sum test and Cohen's effect size calculated to assess for differences between RBC:TP in patient and controls. Results 9 patients (mean age 57±7 years, Male = 6) and 5 volunteers (29 ± 3 years, Female = 5) were enrolled. Patient mean time from hospital discharge was 169, range 116-254 days. There was a difference in RBC:TP between patients and controls (0.3 ± 0.1 versus 0.5 ± 0.1, respectively, p = 0.001, effect size = 1.36). There was significant difference between the RBC and gas phase spectral full width at half maximum (FWHM) between volunteers and patients (median ± 95 % confidence interval, 567 ± 1 vs 507 ± 81, p = 0.002 and 104 ± 2 vs 122 ± 17, p = 0.004, respectively). Results were reproducible with Intraclass Correlation Coefficients of 0.82 and 0.88 for patients and volunteers respectively. Participants had normal or near normal CT scans, mean 7/25, range 0-10/25. Conclusion Xe MRI showed alveolar-capillary diffusion limitation in all 9 post COVID-19 pneumonia patients despite normal or nearly normal CT scans. See also the editorial by Dietrich.

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