BackgroundLong-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments. MethodsEleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data. ResultsNHLC and PHC patients were 287 {+/-} 79 [range 190-437] and 149 {+/-} 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 {+/-} 0.6 [range 0-2] and 7/25 {+/-} 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 {+/-} 8 % vs 86 {+/-} 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBCTP mean between volunteers (0.45 {+/-} 0.07, range [0.33-0.55]) and PHC (0.31 {+/-} 0.11, [range 0.16-0.37]) and NHLC (0.35 {+/-} 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26). ConclusionThere are RBCTP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection. Summary statementHyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal. Key resultsO_LIThere are significant differences in RBCTP mean between healthy controls and PHC/NHLC patients (0.45 {+/-} 0.07, range [0.33-0.55], 0.31 {+/-} 0.11, [range 0.16-0.37], 0.35 {+/-} 0.09, [range 0.26-0.58], respectively, p < 0.05 after correction for multiple comparisons) indicating a change in lung compartment volumes between groups. C_LIO_LIThere was a significant difference in TLco (%) between NHLC and PHC patients (76 {+/-} 8 % vs 86 {+/-} 8%, respectively, p = 0.04), despite normal or near normal FEV (%) (100 {+/-} 13% [range 72-123%] and 88 {+/-} 21% [range 62-113%], p>0.05. C_LIO_LIThere were significant differences in CT abnormalities between NHLC and PHC patients (0.3/25 {+/-} 0.6 [range 0-2] and 7/25 {+/-} 5 [range 4-8], respectively) despite similarly impaired RBCTP. C_LI