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Thesis Format

Integrated Article


Doctor of Philosophy


Medical Biophysics


Parraga, Grace


The COVID-19 pandemic has resulted in millions of global respiratory infections, ranging in severity from asymptomatic to fatal. One of the many consequences of the pandemic is the emergence of long-COVID, which is an umbrella term used to describe the long-term sequelae and poor quality-of-life following recovery from acute COVID-19 infection. However, the pathophysiology and mechanisms responsible for the heterogenous manifestation of long-COVID remain poorly understood. Hyperpolarized 129Xe magnetic resonance imaging (MRI) provides a non-invasive and radiation-free method to regionally visualize and quantify inhaled gas distribution and ventilation in vivo. A strong foundation for the use of pulmonary imaging in asthma and chronic obstructive pulmonary disease (COPD) to strengthen our grasp of disease processes suggests the utility of imaging in long-COVID. Accordingly, the objective of this thesis was to develop a deeper understanding of the structure and function of long-COVID using hyperpolarized 129Xe MRI in tandem with structural computed tomography (CT) imaging. First, we investigated a group of long-COVID participants three months post-infection and observed an increased ventilation defect percent (VDP) in ever- as compared to never-COVID participants. At a follow-up visit one year later, we reported a significant improvement in VDP and the use of airways disease medication increasing the odds of quality-of-life improvement. We then contextualized CT airway sex differences in long-COVID participants by reporting similarities in CT evidence of airway remodelling for females with long-COVID and ex-smokers with and without COPD. Finally, we showed that MRI ventilation textures were predictive of one year improvement in quality-of-life, outperforming VDP and clinical measurements. Taken together, these results suggest an airways disease component to long-COVID that can help guide clinical decision making and improve patient outcomes.

Summary for Lay Audience

The COVID-19 pandemic was very widespread and lead to infections in millions of people around the world. After recovering from COVID-19, many people reported symptoms that did not go away or the inability to return to their normal life, we refer to this as long-COVID. Unfortunately, we still do not completely understand why these people with long-COVID continue to feel poorly. In this thesis, we used structural computed tomography (CT) and functional magnetic resonance imaging (MRI) to better understand which parts of the respiratory system could play a role in long-COVID. First, we found that patients with long-COVID had worse lung ventilation measured on MRI compared to people who were never infected with COVID-19. Then, after one year, we observed these lung ventilation measurements improved and that people who were taking respiratory medication were more likely to improve in their quality-of-life. In addition, we reported that CT measurements of the airways in the lungs are different between male and females with long-COVID, where females with long-COVID have similar measurements to females with chronic respiratory disease. Finally, we showed that patterns and texture of our ventilation MR images could be used to tell us which patients with long-COVID would improve over one year. When we take all these results together, we can say that there is some dysfunction of the airways occurring in people with long-COVID, which can help us better treat these patients.

Creative Commons License

Creative Commons Attribution-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.