Using hyperpolarised xenon magnetic resonance imaging to explore breathlessness in long COVID: results from the EXPLAIN study.

BACKGROUND

Breathlessness is a common symptom in long COVID (LC). Using hyperpolarised xenon magnetic resonance imaging (129Xe-MRI), we assessed whether this symptom could be attributed to abnormalities in the alveolar-capillary membrane not detected by standard investigations. We focused on never-hospitalised individuals without an identified cause for breathlessness.

METHODS

In this prospective, multicentre study, we compared 129Xe-MRI, lung function, exercise capacity and symptom questionnaires in LC patients with breathlessness (BLC) to those without breathlessness (NBLC) and healthy controls. Primary outcome was whether BLC demonstrated measurable impairments in gas exchange focusing on dissolved-phase 129Xe-MRI metrics: red blood cell to membrane ratio (RBC:M) and red blood cell to gas ratio (RBC:Gas). We also explored associations between symptoms and physiological measures.

RESULTS

Of 269 participants recruited, 196 were included in the analysis (109 BLC, 43 NBLC, 44 controls), with age and sex well matched across groups. BLC had a significantly longer interval from infection to MRI (median 632 days; p<0.001). No significant differences in global or regional RBC:M or RBC:Gas were observed across groups. BLC showed lower forced expiratory volume in 1 s, forced vital capacity, transfer factor of the lung for carbon monoxide (T L CO), and carbon monoxide transfer coefficient (K CO) z-scores compared to controls, though >90% of values remained within normal range. A subset of BLC participants with low T L CO (14 out of 109) showed reduced 129Xe-MRI metrics and higher breathlessness scores.

INTERPRETATION: Most nonhospitalised LC participants exhibited no detectable pulmonary abnormalities, including those with breathlessness. However, ∼13% of breathless individuals demonstrated minor reductions in T L CO and 129Xe-MRI gas exchange suggesting a potential pulmonary contribution for symptoms in this subgroup.