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.
- Imaging/CT MRI etc
Data availability statement
Data are available upon reasonable request.
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HKK and MJM are joint first authors.
HKK and MJM contributed equally.
Contributors HKK, MJM, AMM, CV, NR, NBK and SS were responsible for data acquisition. HKK and MJM were responsible for data analysis and for preparing the first draft of the manuscript. EAH and MA assisted with CT acquisition and evaluated the CT data. CV, TH, ID, JN and PN were responsible for recruiting study participants and providing clinical input and interpretation of the data. GES, MSA, AO and MK supported the study design development and interpretation of the data. GP was responsible for study design, data analysis and interpretation as well as being the guarantor of study data integrity. All authors had an opportunity to review and revise the manuscript and approved its final submitted version.
Funding This study was funded by the Ministry of Health and Long-Term Care Ontario. AMM is supported by a Natural Sciences and Engineering Council (Canada) doctoral scholarship. GP, MK and SS are supported by the Canada Research Chair Program. Other contributions: The authors acknowledge the support of the London Health Sciences Centre COVID-19 clinic and Middlesex London Health Unit (which provided all COVID-19 testing and reporting), along with the participants who consented to this 2-year longitudinal study. David Reese, Carol Awde, Shannon Faseruk and Julie Lecomte performed MRI, Angela Wilson, Chynna Huang and Melanie Kjarsgaard were responsible for pulmonary function testing.
Competing interests The authors have reported to BMJ Open Respiratory Research the following: TH has received grants from Fisher & Paykel, honoraria for speaking engagements from AstraZeneca, and has participated on advisory boards for Sanofi, AstraZeneca and Valeo, outside the submitted work. JN has received honoraria for speaking engagements from AstraZeneca, Horizon Therapeutics and Vertix, outside the submitted work. PN has received grants from AstraZeneca, Teva, Sanofi, Foresee and Cyclomedica and personal fees from AstraZeneca, Teva, Equillium, Arrowhead Pharma and GlaxoSmithKline, outside the submitted work. SS has received grants from Cyclomedica, personal fees from Arrowhead Pharma and honoraria for speaking engagements from AstraZeneca, Novartis and Polarean, outside the submitted work. GP has received grants from AstraZeneca and Novartis and honoraria for speaking engagements from AstraZeneca, outside the submitted work. GES, MSA, AO, MK, SS and GP received grants from the Ministry of Health and Long-Term Care Ontario related to this work. HKK, MJM, AMM, CV, NR, EAH, NBK, MA and ID have no conflicts to declare.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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