129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome

BACKGROUND: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised ¹²⁹Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of ¹²⁹Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured ¹²⁹Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS). METHODS: Consenting participants with a confirmed diagnosis of PACS completed ¹²⁹Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed ¹²⁹Xe MRI and pulmonary function tests only. RESULTS: Seventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. ¹²⁹Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO₂ (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO₂ (p=0.03). CONCLUSION: ¹²⁹Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO₂ but not SGRQ or mMRC scores. TRIAL REGISTRATION NUMBER: NCT05014516.