LIVECOVIDFREE: Lung Structure-Function In Survivors of Mild and Severe COVID-19 Infection
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Mild COVID-19 Infection Group 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
Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
Other Names:
Diagnostic Test: Computed Tomography (CT)
Participants will undergo a CT scan of the thoracic cavity
Other Names:
Diagnostic Test: Pulmonary Function Tests (PFT)
Participants will have their lung function evaluated using PFT
Other Names:
Diagnostic Test: Six Minute Walk Test (6MWT)
Participants will perform the six minute walk test as a measure of exercise capacity
Other Names:
Diagnostic Test: Sputum analysis
Participants will provide a sputum sample that will be analysed for eosinophils
Diagnostic Test: Blood analysis
Participants will have their blood drawn and analysed for eosinophil count.
Other: Questionnaires
Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.
|
| Severe COVID-19 Infection Group 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
Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
Other Names:
Diagnostic Test: Computed Tomography (CT)
Participants will undergo a CT scan of the thoracic cavity
Other Names:
Diagnostic Test: Pulmonary Function Tests (PFT)
Participants will have their lung function evaluated using PFT
Other Names:
Diagnostic Test: Six Minute Walk Test (6MWT)
Participants will perform the six minute walk test as a measure of exercise capacity
Other Names:
Diagnostic Test: Sputum analysis
Participants will provide a sputum sample that will be analysed for eosinophils
Diagnostic Test: Blood analysis
Participants will have their blood drawn and analysed for eosinophil count.
Other: Questionnaires
Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.
|
Outcome Measures
Primary Outcome Measures
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by VDP. [1 year]
Measured using 129-Xenon MRI ventilation defect percent
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FEV1. [1 year]
Measured using forced expiratory volume in one second (FEV1)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FVC. [1 year]
Measured using forced vital capacity (FVC)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by TLC. [1 year]
Measured using total lung capacity (TLC)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FRC. [1 year]
Functional residual capacity (FRC)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by RV. [1 year]
Measured using residual volume (RV)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FOT. [1 year]
Measured using forced oscillation technique (FOT)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by LCI. [1 year]
Measured using lung clearance index (LCI)
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FeNO. [1 year]
Measured using Fractional Exhaled Nitric Oxide (FeNO).
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by exercise capacity. [1 year]
Exercise capacity measured by six-minute walk test
- 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 [1 year]
Measured using the baseline dyspnea index questionnaire.
- 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. [1 year]
Measured using the modified medical research council (mMRC) dyspnea scale questionnaire.
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by CAT. [1 year]
Measured using the COPD assessment test (CAT).
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by SGRQ. [1 year]
Measured using the St. George's respiratory questionnaire (SGRQ).
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by IPAQ. [1 year]
Measured using the International Physical Activity Questionnaire (IPAQ).
- Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by eosinophil count. [1 year]
Measured using blood and sputum eosinophil count.
Secondary Outcome Measures
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by VDP. [within 3 months post COVID-19 infection recovery]
Measured using 129-Xenon MRI ventilation defect percent
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FEV1. [within 3 months post COVID-19 infection recovery]
Measured using forced expiratory volume in one second (FEV1).
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FVC. [within 3 months post COVID-19 infection recovery]
Measured using forced vital capacity (FVC)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by TLC. [within 3 months post COVID-19 infection recovery]
Measured using total lung capacity (TLC)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FRC. [within 3 months post COVID-19 infection recovery]
Measured using functional residual capacity (FRC)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by RV. [within 3 months post COVID-19 infection recovery]
Measured using residual volume (RV)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FOT. [within 3 months post COVID-19 infection recovery]
Measured using forced oscillation technique (FOT).
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by LCI. [within 3 months post COVID-19 infection recovery]
Measured using lung clearance index (LCI)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FeNO. [within 3 months post COVID-19 infection recovery]
Measured using Fractional Exhaled Nitric Oxide (FeNO)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by exercise capacity. [within 3 months post COVID-19 infection recovery]
Exercise capacity measured by six-minute walk test
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the baseline dyspnea index questionnaire. [within 3 months post COVID-19 infection recovery]
Measured using the baseline dyspnea index questionnaire.
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the mMRC dyspnea scale questionnaire. [within 3 months post COVID-19 infection recovery]
Measured using the modified medical research council (mMRC) dyspnea scale questionnaire
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by CAT. [within 3 months post COVID-19 infection recovery]
Measured using the COPD assessment test (CAT)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by SGRQ. [within 3 months post COVID-19 infection recovery]
Measured using the St. George's respiratory questionnaire (SGRQ)
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by IPAQ. [within 3 months post COVID-19 infection recovery]
Measured using the International Physical Activity Questionnaire (IPAQ).
- Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by eosinophil count.. [within 3 months post COVID-19 infection recovery]
Measured using blood and sputum eosinophil count.
- Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by sex. [up to 4 years]
Evaluated by assessing different genders.
- Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by age. [up to 4 years]
Evaluated by assessing different age groups.
- Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by smoking history measured in pack-years. [up to 4 years]
Evaluated by assessing smoking history measured in pack-years.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants who are fluent in English reading, understanding and speaking
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Written informed consent must be directly obtained from legally competent participants before any study-related assessment is performed.
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Male and female participants ≥ 18 years and < 80 years.
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Participant experienced a documented case (documented by positive COVID-19 test and/or clinical history) of mild or severe COVID-19 infection.
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Participants are within 3 months post-recovery.
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100 participants will have had mild symptoms.
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100 participants will have had severe symptoms, at least 50 of whom were hospitalized.
Exclusion Criteria:
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Participants meeting contraindications for undergoing an MRI such as participants with MRI-sensitive implants, tattoos with MRI-sensitive dye and severe claustrophobia.
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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.
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Participant is unable to perform spirometry or plethysmography maneuvers.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Medicine (Respirology), McMaster University | Hamilton | Ontario | Canada |
Sponsors and Collaborators
- Western University, Canada
- London Health Sciences Centre
Investigators
- Principal Investigator: Grace E Parraga, PhD, Robarts Research Institute, The University of Western Ontario
Study Documents (Full-Text)
None provided.More Information
Publications
- Driehuys B, Martinez-Jimenez S, Cleveland ZI, Metz GM, Beaver DM, Nouls JC, Kaushik SS, Firszt R, Willis C, Kelly KT, Wolber J, Kraft M, McAdams HP. Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Radiology. 2012 Jan;262(1):279-89. doi: 10.1148/radiol.11102172. Epub 2011 Nov 4.
- Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509.
- Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7.
- Kirby M, Heydarian M, Svenningsen S, Wheatley A, McCormack DG, Etemad-Rezai R, Parraga G. Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation. Acad Radiol. 2012 Feb;19(2):141-52. doi: 10.1016/j.acra.2011.10.007. Epub 2011 Nov 21.
- McGavin CR, Artvinli M, Naoe H, McHardy GJ. Dyspnoea, disability, and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J. 1978 Jul 22;2(6132):241-3.
- Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38.
- Oostveen E, MacLeod D, Lorino H, Farré R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. Review.
- Owrangi AM, Etemad-Rezai R, McCormack DG, Cunningham IA, Parraga G. Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers. Acad Radiol. 2013 May;20(5):537-45. doi: 10.1016/j.acra.2012.11.010.
- Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17.
- Schmidt MH, Marshall J, Downie J, Hadskis MR. Pediatric magnetic resonance research and the minimal-risk standard. IRB. 2011 Sep-Oct;33(5):1-6.
- Shukla Y, Wheatley A, Kirby M, Svenningsen S, Farag A, Santyr GE, Paterson NA, McCormack DG, Parraga G. Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Acad Radiol. 2012 Aug;19(8):941-51. doi: 10.1016/j.acra.2012.03.018. Epub 2012 May 15.
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