EXPLAIN
Research type
Research Study
Full title
Hyperpolarised Xenon Magnetic Resonance PuLmonary Imaging in PAtieNts with Long-COVID (EXPLAIN)
IRAS ID
305846
Contact name
Fergus V Gleeson
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary
We wish to understand why some individuals with long-COVID struggle with breathlessness on exertion (when active) and have a reduced ability to exercise. To do this, we will use MRI scanning and a special gas (hyperpolarised xenon) which is breathed in during the scan. The xenon gas is harmless in the quantity we use. This technique shows the movement of xenon within the lungs and moving out of the lungs into the bloodstream, similar to how oxygen is absorbed. In patients hospitalised with COVID-19, we found that the xenon MRI scans several months after discharge showed lung damage, even when other tests were normal. Importantly, on follow-up imaging, some have remained abnormal.
Our aim is to further our understanding of some of the factors that cause symptoms in Long-COVID, and provide a much needed explanation to individuals struggling with breathlessness. Learning more about the nature of damage within the lungs through xenon MRI may help with the future development of treatments, and provide a reliable way of measuring the treatment response over time.Summary of Results
The main aim of the EXPLAIN study (HypErpolarised Xenon Magnetic Resonance PuLmonary ImAging In PatieNts with Long-COVID) was to investigate whether breathlessness in individuals with Long COVID (LC) is linked to subtle abnormalities in lung gas exchange not detected by standard tests. We used a state-of-the art imaging, called hyperpolarised xenon MRI (¹²⁹Xe-MRI), to assess how effectively gas moves from the lungs into the blood.
The study included 196 participants: those with LC and breathlessness, those with LC but no breathlessness, and healthy controls who had had COVID-19 but fully recovered. We examined the relationship between symptoms, traditional lung function and exercise tests with Xe-MRI.
We found that most LC participants with breathlessness had normal lung imaging and function, although approximately 13% demonstrated minor reductions in diffusing capacity (TLCO) and ¹²⁹Xe-MRI gas exchange metrics.
These findings suggest that for the majority of non-hospitalised LC patients, breathlessness is unlikely to be caused by pulmonary abnormalities. However, a small subgroup may have subtle impairments in alveolar-capillary gas transfer contributing to their symptoms.
In a sub-study of EXPLAIN that ran in parallel to the main study, we examined whether symptoms of Long COVID (LC), including breathlessness, could be linked to abnormal blood clotting or “micro-clots,” a popular theory that has been used to justify treatments like anticoagulants and apheresis.
This part of the study included 173 participants. We undertook detailed analysis of prothrombotic biomarkers and plasma ‘microclots’. Participants again formed three groups – LC with breathlessness, LC without breathlessness and healthy controls. We measured plasma biomarkers associated with blood clotting, blood vessel inflammation, and activation of inflammatory cells and platelets using a laboratory technique called ELISA. Biomarkers included fibrinogen, D-dimer, VWF antigen, p-selectin, sCD40L, PAI-1, and thrombomodulin. We used fluorescent staining and microscopy to look for evidence of microclots (or more accurately, ‘micro-aggregates’) in the blood. We compared the groups and correlated the concentrations of these markers with the data from ¹²⁹Xe-MRI and lung function tests to see if there was an association between blood biomarkers and lung gas exchange.
We found no significant differences in these prothrombotic (or ‘pro-clotting’) biomarkers between groups or the presence and number of micro-aggregates. We found no significant relationship between blood biomarker concentration and lung function values.
These findings suggest that breathlessness in non-hospitalised Long COVID patients is not associated with micro-clots, increased coagulation activity, or lung membrane abnormalities, challenging the theory that LC symptoms are primarily caused by a prothrombotic state.REC name
South Central - Oxford C Research Ethics Committee
REC reference
21/SC/0398
Date of REC Opinion
15 Dec 2021
REC opinion
Further Information Favourable Opinion