Lung Structure-Function In Survivors of Mild and Severe COVID-19 Infection

Study Overview
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Brief Summary
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This is a longitudinal study of the long-term impact of COVID-19 on the lungs. Participants will be followed over a period of up to 4 years and impacts of COVID-19 on the lungs will be measured with magnetic resonance imaging (MRI) using hyperpolarized xenon-129, pulmonary function tests, exercise capacity, computed tomography imaging and questionnaires.

Detailed Description
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This is a multisite longitudinal study of the long-term lung health impact of COVID-19 using hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) over a period of up to 4 years. In total 200 participants age ≥ 18 and <80 years who experienced a documented case of COVID-19 (documented by positive COVID-19 test and/or clinical history) will be screened and recruited if they meet all inclusion criteria at the 5 participating sites. Participants will be grouped in mild or severe COVID-19 infection (100 in each group) including 50 with symptoms and at least 50 participants who were hospitalized with COVID-19 infection, all of whom are within 3 months post recovery and non-infectious. Participants will attend up to 5 study visits over the 4 year period. (Visit 1 within 3 months post-COVID-19 recovery, Visit 2 at 24 ± 4 weeks, Visit 3 at 48 ± 4 weeks, Visit 4 at 78 ± 4 weeks, Visit 5 at 200 ± 16 weeks) At all visits, participants will complete 129Xe MRI, questionnaires (St. George's Respiratory Questionnaire, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Modified Borg Scale Breathlessness and Fatigue Questionnaire, Baseline Dyspnea Index Questionnaire and International Physical Activity Questionnaire), pulmonary function tests (Spirometry, Plethysmography, Forced Oscillation Technique, Fractional Exhaled Nitric Oxide, and Multiple Breath Nitrogen Washout), blood and sputum analysis, exercise testing (six-minute walk test). At Visit 1, participants will also complete computed tomography imaging at University Hospital, London Health Sciences Centre. Visits 2 and 4 have the option of being completed over the phone, in which case only questionnaires will be completed. Visit 5 is an optional 4-year follow-up.

Official Title
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Lung Structure-Function In SurVivors of Mild and SEvere COVID-19 Infection: 129Xe MRI and CT For Rapid Evaluations and NExt-wave Healthcare Planning

Conditions
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Covid19

Intervention / Treatment
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* Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs
* Diagnostic Test: Computed Tomography (CT)
* Diagnostic Test: Pulmonary Function Tests (PFT)
* Diagnostic Test: Six Minute Walk Test (6MWT)
* Diagnostic Test: Sputum analysis
* Diagnostic Test: Blood analysis
* Other: Questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are fluent in English reading, understanding and speaking Written informed consent must be directly obtained from legally competent participants before any study-related assessment is performed. Male and female participants ≥ 18 years and < 80 years. Participant experienced a documented case (documented by positive COVID-19 test and/or clinical history) of mild or severe COVID-19 infection. Participants are within 3 months post-recovery. 100 participants will have had mild symptoms. 100 participants will have had severe symptoms, at least 50 of whom were hospitalized. Exclusion Criteria: Participants meeting contraindications for undergoing an MRI such as participants with MRI-sensitive implants, tattoos with MRI-sensitive dye and severe claustrophobia. Participant is, in the opinion of the Investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material. Participant is unable to perform spirometry or plethysmography maneuvers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mild COVID-19 Infection Group<br>100 participants age ≥ 18 and <80 years who experienced a documented case (documented by positive COVID-19 test and/or clinical history) of mild COVID-19 infection, all of whom are within 3 months post recovery and non-infectious. | Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs<br>* Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas<br>* Other names: 129Xe MRI;Diagnostic Test: Computed Tomography (CT)<br>* Participants will undergo a CT scan of the thoracic cavity<br>* Other names: CT;Diagnostic Test: Pulmonary Function Tests (PFT)<br>* Participants will have their lung function evaluated using PFT<br>* Other names: PFT;Diagnostic Test: Six Minute Walk Test (6MWT)<br>* Participants will perform the six minute walk test as a measure of exercise capacity<br>* Other names: 6MWT;Diagnostic Test: Sputum analysis<br>* Participants will provide a sputum sample that will be analysed for eosinophils<br>Diagnostic Test: Blood analysis<br>* Participants will have their blood drawn and analysed for eosinophil count.<br>Other: Questionnaires<br>* Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.<br>|
| Severe COVID-19 Infection Group<br>100 participants age ≥ 18 and <80 years who experienced a documented case (documented by positive COVID-19 test and/or clinical history) of severe COVID-19 infection, including at least 50 participants who were hospitalized with COVID-19 infection, all of whom are within 3 months post recovery and non-infectious. | Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs<br>* Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas<br>* Other names: 129Xe MRI;Diagnostic Test: Computed Tomography (CT)<br>* Participants will undergo a CT scan of the thoracic cavity<br>* Other names: CT;Diagnostic Test: Pulmonary Function Tests (PFT)<br>* Participants will have their lung function evaluated using PFT<br>* Other names: PFT;Diagnostic Test: Six Minute Walk Test (6MWT)<br>* Participants will perform the six minute walk test as a measure of exercise capacity<br>* Other names: 6MWT;Diagnostic Test: Sputum analysis<br>* Participants will provide a sputum sample that will be analysed for eosinophils<br>Diagnostic Test: Blood analysis<br>* Participants will have their blood drawn and analysed for eosinophil count.<br>Other: Questionnaires<br>* Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by VDP. | Measured using 129-Xenon MRI ventilation defect percent | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FEV1. | Measured using forced expiratory volume in one second (FEV1) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FVC. | Measured using forced vital capacity (FVC) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by TLC. | Measured using total lung capacity (TLC) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FRC. | Functional residual capacity (FRC) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by RV. | Measured using residual volume (RV) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FOT. | Measured using forced oscillation technique (FOT) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by LCI. | Measured using lung clearance index (LCI) | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FeNO. | Measured using Fractional Exhaled Nitric Oxide (FeNO). | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by exercise capacity. | Exercise capacity measured by six-minute walk test | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by baseline dyspnea index questionnaire | Measured using the baseline dyspnea index questionnaire. | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by (mMRC) dyspnea scale questionnaire. | Measured using the modified medical research council (mMRC) dyspnea scale questionnaire. | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by CAT. | Measured using the COPD assessment test (CAT). | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by SGRQ. | Measured using the St. George's respiratory questionnaire (SGRQ). | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by IPAQ. | Measured using the International Physical Activity Questionnaire (IPAQ). | 1 year | 
| Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by eosinophil count. | Measured using blood and sputum eosinophil count. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by VDP. | Measured using 129-Xenon MRI ventilation defect percent | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FEV1. | Measured using forced expiratory volume in one second (FEV1). | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FVC. | Measured using forced vital capacity (FVC) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by TLC. | Measured using total lung capacity (TLC) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FRC. | Measured using functional residual capacity (FRC) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by RV. | Measured using residual volume (RV) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FOT. | Measured using forced oscillation technique (FOT). | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by LCI. | Measured using lung clearance index (LCI) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FeNO. | Measured using Fractional Exhaled Nitric Oxide (FeNO) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by exercise capacity. | Exercise capacity measured by six-minute walk test | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the baseline dyspnea index questionnaire. | Measured using the baseline dyspnea index questionnaire. | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the mMRC dyspnea scale questionnaire. | Measured using the modified medical research council (mMRC) dyspnea scale questionnaire | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by CAT. | Measured using the COPD assessment test (CAT) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by SGRQ. | Measured using the St. George's respiratory questionnaire (SGRQ) | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by IPAQ. | Measured using the International Physical Activity Questionnaire (IPAQ). | within 3 months post COVID-19 infection recovery | 
| Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by eosinophil count.. | Measured using blood and sputum eosinophil count. | within 3 months post COVID-19 infection recovery | 
| Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by sex. | Evaluated by assessing different genders. | up to 4 years | 
| Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by age. | Evaluated by assessing different age groups. | up to 4 years | 
| Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by smoking history measured in pack-years. | Evaluated by assessing smoking history measured in pack-years. | up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Pulmonary Function, Xenon-129, Magnetic Resonance Imaging