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NCT Number: NCT04584671

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Medicine (Respirology), McMaster University

Hamilton, Ontario, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Hyperpolarized Xenon-129 MRI of the lungs

Diagnostic Test

Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas

Other names: 129Xe MRI

Computed Tomography (CT)

Diagnostic Test

Participants will undergo a CT scan of the thoracic cavity

Other names: CT

Pulmonary Function Tests (PFT)

Diagnostic Test

Participants will have their lung function evaluated using PFT

Other names: PFT

Six minute walk test (6MWT)

Diagnostic Test

Participants will perform the six minute walk test as a measure of exercise capacity

Other names: 6MWT

Sputum analysis

Diagnostic Test

Participants will provide a sputum sample that will be analysed for eosinophils

Blood analysis

Diagnostic Test

Participants will have their blood drawn and analysed for eosinophil count.

questionnaires

Other

Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.

Primary outcomes

  1. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by VDP.

    Time frame: 1 year

    Measured using 129-Xenon MRI ventilation defect percent

  2. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FEV1.

    Time frame: 1 year

    Measured using forced expiratory volume in one second (FEV1)

  3. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FVC.

    Time frame: 1 year

    Measured using forced vital capacity (FVC)

  4. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by TLC.

    Time frame: 1 year

    Measured using total lung capacity (TLC)

  5. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FRC.

    Time frame: 1 year

    Functional residual capacity (FRC)

  6. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by RV.

    Time frame: 1 year

    Measured using residual volume (RV)

  7. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FOT.

    Time frame: 1 year

    Measured using forced oscillation technique (FOT)

  8. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by LCI.

    Time frame: 1 year

    Measured using lung clearance index (LCI)

  9. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FeNO.

    Time frame: 1 year

    Measured using Fractional Exhaled Nitric Oxide (FeNO).

  10. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by exercise capacity.

    Time frame: 1 year

    Exercise capacity measured by six-minute walk test

  11. 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

    Time frame: 1 year

    Measured using the baseline dyspnea index questionnaire.

  12. 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.

    Time frame: 1 year

    Measured using the modified medical research council (mMRC) dyspnea scale questionnaire.

  13. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by CAT.

    Time frame: 1 year

    Measured using the COPD assessment test (CAT).

  14. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by SGRQ.

    Time frame: 1 year

    Measured using the St. George's respiratory questionnaire (SGRQ).

  15. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by IPAQ.

    Time frame: 1 year

    Measured using the International Physical Activity Questionnaire (IPAQ).

  16. Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by eosinophil count.

    Time frame: 1 year

    Measured using blood and sputum eosinophil count.

Secondary outcomes

  1. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by VDP.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using 129-Xenon MRI ventilation defect percent

  2. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FEV1.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using forced expiratory volume in one second (FEV1).

  3. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FVC.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using forced vital capacity (FVC)

  4. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by TLC.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using total lung capacity (TLC)

  5. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FRC.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using functional residual capacity (FRC)

  6. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by RV.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using residual volume (RV)

  7. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FOT.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using forced oscillation technique (FOT).

  8. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by LCI.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using lung clearance index (LCI)

  9. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FeNO.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using Fractional Exhaled Nitric Oxide (FeNO)

  10. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by exercise capacity.

    Time frame: within 3 months post COVID-19 infection recovery

    Exercise capacity measured by six-minute walk test

  11. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the baseline dyspnea index questionnaire.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using the baseline dyspnea index questionnaire.

  12. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the mMRC dyspnea scale questionnaire.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using the modified medical research council (mMRC) dyspnea scale questionnaire

  13. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by CAT.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using the COPD assessment test (CAT)

  14. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by SGRQ.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using the St. George's respiratory questionnaire (SGRQ)

  15. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by IPAQ.

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using the International Physical Activity Questionnaire (IPAQ).

  16. Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by eosinophil count..

    Time frame: within 3 months post COVID-19 infection recovery

    Measured using blood and sputum eosinophil count.

  17. Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by sex.

    Time frame: up to 4 years

    Evaluated by assessing different genders.

  18. Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by age.

    Time frame: up to 4 years

    Evaluated by assessing different age groups.

  19. Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by smoking history measured in pack-years.

    Time frame: up to 4 years

    Evaluated by assessing smoking history measured in pack-years.

Sponsors and collaborators

Lead sponsor

Western University, Canada

Other

Collaborators

  • London Health Sciences Centre

Registry information

Official study title

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

Acronym: LIVECOVIDFREE

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Oct 14, 2020
Registry last updated
Aug 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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