The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID
Authors: Grist James T. , Collier Guilhem J. , Walters Huw , Chen Mitchell , Eid Gabriele Abu , Laws Aviana , Matthews Violet , Jacob Kenneth , Cross Susan , Eves Alexandra , Durant Marianne , Mcintyre Anthony , Thompson Roger , Schulte Rolf F. , Raman Betty , Robbins Peter A. , Wild Jim M. , Fraser Emily , Gleeson Fergus 
Published: February 2022

Background

Long-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.

Methods

Eleven 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.

Results

NHLC 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 RBC:TP 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).

Conclusion

There are RBC:TP 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 statement

Hyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal.

Key results

There are significant differences in RBC:TP 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.

There 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.

There 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 RBC:TP.