COVID-19 Related Lung Ventilation and Perfusion Injury

Study Overview
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Brief Summary
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Little is currently known about the immediate and long-term effect of COVID-19 on lung ventilation (delivery of air to the lungs) and lung perfusion (delivery of blood to the lungs). Some people who survive COVID-19 may have lung ventilation and/or perfusion injury that persists following COVID-19 recovery. This lung injury may be related to inflammation in the lung, breathlessness, exercise limitation and reduced quality of life. Therefore, towards the goal of understanding the effects of COVID-19 on lung health, the purpose of this study is to characterize and understand the clinical relevance of COVID-19 related lung ventilation and perfusion injury and associated inflammatory status, ≤4 weeks and 6-months following COVID-19 recovery in an asthmatic and healthy population. To do this, an asthmatic and healthy population who have, and have not, been previously diagnosed with COVID-19 will be studied.

Official Title
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Prospective Longitudinal Study to Characterize and Understand the Clinical Relevance of SARS-CoV2 Related Ventilation and Perfusion Injury Evaluated by V/Q SPECT-CT in an Asthmatic and Healthy Population

Conditions
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Covid-19, Asthma, Healthy

Intervention / Treatment
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* Other: V/Q SPECT-CT
* Other: St. George's Respiratory Questionnaire (SGRQ)
* Other: mMRC (Modified Medical Research Council) Dyspnea Scale
* Other: Six-minute walk test (6MWT)
* Other: Spirometry
* Other: Plethysmography & DLCO
* Other: Airwave Oscillometry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all participants: Males and females ≥ 18 years of age Individuals able and willing to provide written informed consent Individuals able and willing to comply with the study protocol For participants with asthma: Individuals with physician confirmed asthma (12% bronchodilator reversibility or PC20 methacholine less than 8mg/ml) Individuals treated with inhaled corticosteroids, oral corticosteroids and/or anti-T2 biologics For participants who recently recovered from covid-19: Individuals previously diagnosed with covid-19 confirmed by FLOQswab test Individuals who recently (≤4-weeks) recovered from covid-19 Exclusion Criteria: For all participants: Males and females < 18 years of age Individuals who are unable to read and/or understand English Individuals who are pregnant or breastfeeding Individuals who currently smoke or are an ex-smoker with ≥10 pack-year smoking history Individuals who in the opinion of the investigator, are mentally or legally incapacitated, preventing informed consent from being obtained Individuals who are unable to complete one or more study manoeuvres For participants with no history of lung disease: Individuals with a history of respiratory infection or disease For participants who have not been diagnosed with covid-19: Individuals who have previously had covid-19 confirmed by FLOQswab test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| healthy COVID-19+<br>Individuals who recently recovered from COVID-19 and who have no history of lung disease | Other: V/Q SPECT-CT<br>* At visits 1 and 2, ventilation will be assessed by 99mTc Technegas SPECT ventilation scan and perfusion will be assessed by 99mTc Macroaggregated Albumin SPECT perfusion scan.<br>Other: St. George's Respiratory Questionnaire (SGRQ)<br>* At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).<br>Other: mMRC (Modified Medical Research Council) Dyspnea Scale<br>* At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.<br>Other: Six-minute walk test (6MWT)<br>* At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).<br>Other: Spirometry<br>* At visits 1 and 2, spirometry will be performed to quantify the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and FEV1/FVC.<br>Other: Plethysmography & DLCO<br>* At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.<br>Other: Airwave Oscillometry<br>* At visits 1 and 2, airwave oscillometry will be performed to obtain resistance (R) and reactance (X) at 5 Hz (R5) and 19 Hz (R19). The resonance frequency (fres), area above the reactance curve (AX) and the heterogeneity of obstruction (R5-19) will be derived from R and X.<br>|
| asthmatic COVID-19+<br>Individuals who recently recovered from COVID-19 and who have asthma | Other: V/Q SPECT-CT<br>* At visits 1 and 2, ventilation will be assessed by 99mTc Technegas SPECT ventilation scan and perfusion will be assessed by 99mTc Macroaggregated Albumin SPECT perfusion scan.<br>Other: St. George's Respiratory Questionnaire (SGRQ)<br>* At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).<br>Other: mMRC (Modified Medical Research Council) Dyspnea Scale<br>* At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.<br>Other: Six-minute walk test (6MWT)<br>* At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).<br>Other: Spirometry<br>* At visits 1 and 2, spirometry will be performed to quantify the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and FEV1/FVC.<br>Other: Plethysmography & DLCO<br>* At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.<br>Other: Airwave Oscillometry<br>* At visits 1 and 2, airwave oscillometry will be performed to obtain resistance (R) and reactance (X) at 5 Hz (R5) and 19 Hz (R19). The resonance frequency (fres), area above the reactance curve (AX) and the heterogeneity of obstruction (R5-19) will be derived from R and X.<br>|
| healthy COVID-19-<br>Individuals who have not been diagnosed with COVID-19 and who have no history of lung disease | Other: V/Q SPECT-CT<br>* At visits 1 and 2, ventilation will be assessed by 99mTc Technegas SPECT ventilation scan and perfusion will be assessed by 99mTc Macroaggregated Albumin SPECT perfusion scan.<br>Other: St. George's Respiratory Questionnaire (SGRQ)<br>* At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).<br>Other: mMRC (Modified Medical Research Council) Dyspnea Scale<br>* At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.<br>Other: Six-minute walk test (6MWT)<br>* At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).<br>Other: Spirometry<br>* At visits 1 and 2, spirometry will be performed to quantify the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and FEV1/FVC.<br>Other: Plethysmography & DLCO<br>* At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.<br>Other: Airwave Oscillometry<br>* At visits 1 and 2, airwave oscillometry will be performed to obtain resistance (R) and reactance (X) at 5 Hz (R5) and 19 Hz (R19). The resonance frequency (fres), area above the reactance curve (AX) and the heterogeneity of obstruction (R5-19) will be derived from R and X.<br>|
| asthmatic COVID-19-<br>Individuals who have not been diagnosed with COVID-19 and who have asthma | Other: V/Q SPECT-CT<br>* At visits 1 and 2, ventilation will be assessed by 99mTc Technegas SPECT ventilation scan and perfusion will be assessed by 99mTc Macroaggregated Albumin SPECT perfusion scan.<br>Other: St. George's Respiratory Questionnaire (SGRQ)<br>* At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).<br>Other: mMRC (Modified Medical Research Council) Dyspnea Scale<br>* At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.<br>Other: Six-minute walk test (6MWT)<br>* At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).<br>Other: Spirometry<br>* At visits 1 and 2, spirometry will be performed to quantify the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and FEV1/FVC.<br>Other: Plethysmography & DLCO<br>* At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.<br>Other: Airwave Oscillometry<br>* At visits 1 and 2, airwave oscillometry will be performed to obtain resistance (R) and reactance (X) at 5 Hz (R5) and 19 Hz (R19). The resonance frequency (fres), area above the reactance curve (AX) and the heterogeneity of obstruction (R5-19) will be derived from R and X.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term difference in ventilation defect percent assessed by ventilation SPECT-CT - healthy | The short-term difference in lung ventilation between healthyCOVID-19+ and healthyCOVID-19- participants | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Short-term difference in perfusion defect percent assessed by perfusion SPECT-CT - healthy | The short-term difference in lung perfusion between healthyCOVID-19+ and healthyCOVID-19- participants | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Short-term difference in lung ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - healthy | The short-term difference in lung ventilation/perfusion mismatch between healthyCOVID-19+ and healthyCOVID-19- participants | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Long-term difference in ventilation defect percent assessed by ventilation SPECT-CT - healthy | The long-term difference in lung ventilation between healthyCOVID-19+ and healthyCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Long-term difference in perfusion defect percent assessed by perfusion SPECT-CT - healthy | The long-term difference in lung perfusion between healthyCOVID-19+ and healthyCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Long-term difference in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - healthy | The long-term difference in lung ventilation/perfusion mismatch between healthyCOVID-19+ and healthyCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Short-term difference in ventilation defect percent assessed by ventilation SPECT-CT - asthmatic | The short-term difference in lung ventilation between asthmaticCOVID-19+ and asthmaticCOVID-19- participants | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Short-term difference in perfusion defect percent assessed by perfusion SPECT-CT - asthmatic | The short-term difference in lung perfusion between asthmaticCOVID-19+ and asthmaticCOVID-19- participants | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Short-term difference in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - asthmatic | The short-term difference in lung ventilation/perfusion mismatch between asthmaticCOVID-19+ and asthmaticCOVID-19- participants | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Long-term difference in ventilation defect percent assessed by ventilation SPECT-CT - asthmatic | The long-term difference in lung ventilation between asthmaticCOVID-19+ and asthmaticCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Long-term difference in perfusion defect percent assessed by perfusion SPECT-CT - asthmatic | The long-term difference in lung perfusion between asthmaticCOVID-19+ and asthmaticCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Long-term difference in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - asthmatic | The long-term difference in lung ventilation/perfusion mismatch between asthmaticCOVID-19+ and asthmaticCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Longitudinal change in ventilation defect percent assessed by ventilation SPECT-CT - healthy | Difference in the 6-month change in lung ventilation between healthyCOVID-19+ and healthyCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Longitudinal change in perfusion defect percent assessed by perfusion SPECT-CT - healthy | Difference in the 6-month change in lung perfusion between healthyCOVID-19+ and healthyCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Longitudinal change in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - healthy | Difference in the 6-month change in lung ventilation/perfusion mismatch between healthyCOVID-19+ and healthyCOVID-19- participants | 6-months post COVID-19 recovery (Visit 2) | 
| Longitudinal change in ventilation defect percent assessed by ventilation SPECT-CT - asthmatic | Difference in the 6-month change in lung ventilation between asthmaticCOVID-19+ and asthmaticCOVID-19- participants. | 6-months post COVID-19 recovery (Visit 2) | 
| Longitudinal change in perfusion defect percent assessed by perfusion SPECT-CT - asthmatic | Difference in the 6-month change in lung perfusion between asthmaticCOVID-19+ and asthmaticCOVID-19- participants. | 6-months post COVID-19 recovery (Visit 2) | 
| Longitudinal change in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - asthmatic | Difference in the 6-month change in lung ventilation/perfusion mismatch between asthmaticCOVID-19+ and asthmaticCOVID-19- participants. | 6-months post COVID-19 recovery (Visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of lung ventilation with the St. George's Respiratory Questionnaire (SGRQ) score ≤4-weeks post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with the St. George's Respiratory Questionnaire (SGRQ) score ≤4-weeks post COVID-19 recovery (Visit 1). | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Correlation of lung ventilation with six-minute walk distance (6MWD) ≤4-weeks post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with six-minute walk distance (6MWD) ≤4-weeks post COVID-19 recovery (Visit 1). | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Correlation of lung ventilation with the forced expiratory volume in one second (FEV1) ≤4-weeks post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with the forced expiratory volume in one second (FEV1) ≤4-weeks post COVID-19 recovery (Visit 1). | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Correlation of lung ventilation with the diffusing capacity of the lung for carbon monoxide (DLCO) ≤4-weeks post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with the diffusing capacity of the lung for carbon monoxide (DLCO) ≤4-weeks post COVID-19 recovery (Visit 1). | ≤4-weeks post COVID-19 recovery (Visit 1) | 
| Correlation of lung ventilation with the St. George's Respiratory Questionnaire (SGRQ) score 6-months post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with the St. George's Respiratory Questionnaire (SGRQ) score 6-months post COVID-19 recovery (Visit 2). | 6-months post COVID-19 recovery (Visit 2) | 
| Correlation of lung ventilation with six-minute walk distance (6MWD) 6-months post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with six-minute walk distance (6MWD) 6-months post COVID-19 recovery (Visit 2). | 6-months post COVID-19 recovery (Visit 2) | 
| Correlation of lung ventilation with the forced expiratory volume in one second (FEV1) 6-months post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with the forced expiratory volume in one second (FEV1) 6-months post COVID-19 recovery (Visit 2). | 6-months post COVID-19 recovery (Visit 2) | 
| Correlation of lung ventilation with the diffusing capacity of the lung for carbon monoxide (DLCO) 6-months post COVID-19 recovery | In COVID-19+ participants, the correlation of lung ventilation with the diffusing capacity of the lung for carbon monoxide (DLCO) 6-months post COVID-19 recovery (Visit 2). | 6-months post COVID-19 recovery (Visit 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid-19, lung ventilation, lung perfusion, V/Q SPECT, lung health, Technegas