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

Active, not recruiting

• Conditions: Covid19
• Interventions: 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

• Registration Number: NCT04584671
• Lead Sponsor: Western University, Canada

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.

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 Timeline

• Study First Submitted: 2020-10-07
• Study First Submitted QC: 2020-10-09
• Study First Posted: 2020-10-14
• Study Start: 2021-01-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-22
• Last Update Posted: 2024-04-23
• Primary Completion: 2025-06-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Mild COVID-19 Infection Group	Pulmonary Function Tests (PFT)	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.
Mild COVID-19 Infection Group	Computed Tomography (CT)	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.
Severe COVID-19 Infection Group	Questionnaires	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.
Mild COVID-19 Infection Group	Six Minute Walk Test (6MWT)	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.
Severe COVID-19 Infection Group	Six Minute Walk Test (6MWT)	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.
Severe COVID-19 Infection Group	Blood analysis	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.
Mild COVID-19 Infection Group	Sputum analysis	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.
Severe COVID-19 Infection Group	Computed Tomography (CT)	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.
Mild COVID-19 Infection Group	Questionnaires	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.
Mild COVID-19 Infection Group	Hyperpolarized Xenon-129 MRI of the lungs	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.
Severe COVID-19 Infection Group	Pulmonary Function Tests (PFT)	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.
Severe COVID-19 Infection Group	Sputum analysis	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.
Mild COVID-19 Infection Group	Blood analysis	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.
Severe COVID-19 Infection Group	Hyperpolarized Xenon-129 MRI of the lungs	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.

Primary Outcome Measures

Name	Time	Method
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 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 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 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 (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 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 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 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 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 eosinophil count.	1 year	Measured using blood and sputum eosinophil count.
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 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 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 CAT.	1 year	Measured using the COPD assessment test (CAT).

Secondary Outcome Measures

Name	Time	Method
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 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 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 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 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 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.
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 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 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 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 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 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 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 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 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 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.

Trial Locations

Locations (1)

Department of Medicine (Respirology), McMaster University; 🇨🇦 Hamilton, Ontario, Canada