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Respiratory research
129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome
  1. Harkiran K Kooner1,2,
  2. Marrissa J McIntosh1,2,
  3. Alexander M Matheson1,2,
  4. Carmen Venegas3,4,
  5. Nisarg Radadia4,
  6. Terence Ho3,4,
  7. Ehsan Ahmed Haider5,
  8. Norman B Konyer6,
  9. Giles E Santyr7,8,
  10. Mitchell S Albert9,10,
  11. Alexei Ouriadov11,
  12. Mohamed Abdelrazek12,
  13. Miranda Kirby13,
  14. Inderdeep Dhaliwal14,
  15. J Michael Nicholson14,
  16. Parameswaran Nair3,4,
  17. Sarah Svenningsen3,4 and
  18. Grace Parraga1,2,14
  1. 1Robarts Research Institute, Western University, London, Ontario, Canada
  2. 2Department of Medical Biophysics, Western University, London, Ontario, Canada
  3. 3Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario, Canada
  4. 4Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  5. 5Department of Radiology, McMaster University, Hamilton, Ontario, Canada
  6. 6Imaging Research Centre, St. Joseph's Healthcare, Hamilton, Ontario, Canada
  7. 7The Hospital for Sick Children, Toronto, Ontario, Canada
  8. 8Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
  9. 9Department of Chemistry, Lakehead University, Thunder Bay, Ontario, Canada
  10. 10Thunder Bay Regional Health Research Institute, Thunder Bay, Ontario, Canada
  11. 11Department of Physics and Astronomy, Western University, London, Ontario, Canada
  12. 12Department of Medical Imaging, Western University, London, Ontario, Canada
  13. 13Department of Physics, Ryerson University, Toronto, Ontario, Canada
  14. 14Division of Respirology, Department of Medicine, Western University, London, Ontario, Canada
  1. Correspondence to Dr Grace Parraga; gparraga{at}robarts.ca

Abstract

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.

  • COVID-19
  • Imaging/CT MRI etc

Data availability statement

Data are available upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

http://dx.doi.org/10.1136/bmjresp-2022-001235

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • 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.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.