Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1H and 129Xe lung MRI

Introduction Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pathophysiological pulmonary changes during the post-acute period in these patients remains unclear. Methods Patients who were hospitalised due to COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25 and 51 weeks after hospital admission. The imaging protocol included: ultra-short echo time, dynamic contrast enhanced lung perfusion, 129Xe lung ventilation, 129Xe diffusion weighted and 129Xe 3D spectroscopic imaging of gas exchange. Results 9 patients were recruited and underwent MRI at 6 (n=9), 12 (n=9), 25 (n=6) and 51 (n=8) weeks after hospital admission. Patients with signs of interstitial lung damage at 3 months were excluded from this study. At 6 weeks after hospital admission, patients demonstrated impaired 129Xe gas transfer (RBC:M) but normal lung microstructure (ADC, LmD). Minor ventilation abnormalities present in four patients were largely resolved in the 6–25 week period. At 12 week follow up, all patients with lung perfusion data available (n=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 week follow up, significant improvements in 129Xe gas transfer were observed compared to 6-week examinations, however 129Xe gas transfer remained abnormally low at weeks 12, 25 and 51. Changes in 129Xe gas transfer correlated significantly with changes in pulmonary blood volume and TLCO Z-score. Conclusions This study demonstrates that multinuclear MRI is sensitive to functional pulmonary changes in the follow up of patients who were hospitalised with COVID-19. Impairment of xenon transfer may indicate damage to the pulmonary microcirculation. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. L Saunders, G Collier, HF Chan, L Smith, J Watson, J Meiring, Z Gabriel, T Newman, M Plowright, J A Eaden, J Bray, D Capener, L Armstrong, J Rodgers, M Brook, AM Biancardi, G Norquay, O Rodgers, R Munro, N Stewart, J Grist, S Rajaram, GH Mills and P Collini declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work. The following authors have declarations of support from organisations for the submitted work: PJC Hughes receives grant funding from GlaxoSmithKline and Bayer. AAR Thompson is funded by British Heart Foundation Intermediate Clinical Fellowship and grant funding from Janssen-Cilag Ltd. A Lawrie receives grant funding from the British Heart Foundation (fellowship award). G Jenkins receives grant funding from Astra Zeneca, Biogen, Galecto, GlaxoSmithKline, RedX, Pliant, Genetech. A Swift receives grant funding from NIHR (AI award), Wellcome (Innovator award) and Janssen-Cilag Ltd (project grant). J Wild receives grant funding from MRC, GSK (investigator led research grant) and GE Healthcare. F Gleeson recieives grant or contract funding from Oxford NIHR BRC, NIHR (EXPLAIN trial), POLAREAN Ltd and GE Healthcare. K Johnson received grant support from NIH. The following authors declare financial relationships with organisations that might have an interest in the submitted work in the previous three years: A Cahn is an employee of GSK. FJ Wilson was an employee of GSK at the time of the study. A Cahn is a shareholder in GlaxoSmithKline, FJ Wilson was a shareholder in GlaxoSmithKline at the time of the study. RF Schulte is an employee of GE Healthcare. A Lawrie receives funding support from Janssen-Cilag Ltd for meetings/travel. AAR Thompson funding from Janssen-Cilag Ltd for meetings/travel. G Jenkins receives consulting fees from Bristol Myers Squibb, Daewoong, Veracyte, Resolution Therapeutics, RedX, Pliant, Chiesi. A Swift receives consultancy fees from Janssen-Cilag Ltd. Payment for lectures/speaker fees/educational events: G Jenkins receives payment from Chiesi, Roche, PatientMPower, AstraZeneca, GSK, Boehringer Ingelheim for lecturers. A Swift receives payment from Janssen-Cilag Ltd. F Gleeson receives payment from POLAREAN Ltd. Leadship roles in related boards, societies or committees: G Jenkins is a trustee of Action for Pulmonary Fibrosis. F Gleeson is the president of the European society for thoracic imaging. ### Funding Statement JMW Medical Research Council grant MR/M008894/1 GSK and GE for investigator led grant funding AART was supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: London - Hampstead Research Ethics Committee gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors