COVID-19 Related Lung Ventilation and Perfusion Injury

• ClinicalTrials.gov Identifier: NCT04549636
• Recruitment Status: Recruiting
• First Posted: September 16, 2020
• Last Update Posted: September 10, 2021
• Sponsor: McMaster University
• Collaborators: Research St. Joseph's - Hamilton; Cyclomedica Australia Pty Ltd
• Information provided by (Responsible Party): McMaster University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Covid-19; Asthma; Healthy	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

Study Design

• Study Type: Observational
• Estimated Enrollment: 92 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: 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
• Actual Study Start Date: October 18, 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
healthy COVID-19+; Individuals who recently recovered from COVID-19 and who have no history of lung disease	Other: V/Q SPECT-CT; 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.; Other: St. George's Respiratory Questionnaire (SGRQ); At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).; Other: mMRC (Modified Medical Research Council) Dyspnea Scale; At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.; Other: Six-minute walk test (6MWT); At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).; Other: Spirometry; 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.; Other: Plethysmography & DLCO; At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.; Other: Airwave Oscillometry; 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.
asthmatic COVID-19+; Individuals who recently recovered from COVID-19 and who have asthma	Other: V/Q SPECT-CT; 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.; Other: St. George's Respiratory Questionnaire (SGRQ); At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).; Other: mMRC (Modified Medical Research Council) Dyspnea Scale; At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.; Other: Six-minute walk test (6MWT); At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).; Other: Spirometry; 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.; Other: Plethysmography & DLCO; At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.; Other: Airwave Oscillometry; 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.
healthy COVID-19-; Individuals who have not been diagnosed with COVID-19 and who have no history of lung disease	Other: V/Q SPECT-CT; 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.; Other: St. George's Respiratory Questionnaire (SGRQ); At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).; Other: mMRC (Modified Medical Research Council) Dyspnea Scale; At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.; Other: Six-minute walk test (6MWT); At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).; Other: Spirometry; 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.; Other: Plethysmography & DLCO; At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.; Other: Airwave Oscillometry; 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.
asthmatic COVID-19-; Individuals who have not been diagnosed with COVID-19 and who have asthma	Other: V/Q SPECT-CT; 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.; Other: St. George's Respiratory Questionnaire (SGRQ); At visits 1 and 2, quality of life will be evaluated using the St. George's Respiratory Questionnaire (SGRQ).; Other: mMRC (Modified Medical Research Council) Dyspnea Scale; At visits 1 and 2, dyspnea will be evaluated using the mMRC (Modified Medical Research Council) Dyspnea Scale.; Other: Six-minute walk test (6MWT); At visits 1 and 2, exercise capacity will be evaluated using the six-minute walk test (6MWT).; Other: Spirometry; 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.; Other: Plethysmography & DLCO; At visits 1 and 2, plethysmography and the diffusing capacity of the lung for carbon monoxide (DLCO) will be performed.; Other: Airwave Oscillometry; 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.

Outcome Measures

Primary Outcome Measures :

1. Short-term difference in ventilation defect percent assessed by ventilation SPECT-CT - healthy [ Time Frame: ≤4-weeks post COVID-19 recovery (Visit 1) ]
   The short-term difference in lung ventilation between healthyCOVID-19+ and healthyCOVID-19- participants
2. Short-term difference in perfusion defect percent assessed by perfusion SPECT-CT - healthy [ Time Frame: ≤4-weeks post COVID-19 recovery (Visit 1) ]
   The short-term difference in lung perfusion between healthyCOVID-19+ and healthyCOVID-19- participants
3. Short-term difference in lung ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - healthy [ Time Frame: ≤4-weeks post COVID-19 recovery (Visit 1) ]
   The short-term difference in lung ventilation/perfusion mismatch between healthyCOVID-19+ and healthyCOVID-19- participants
4. Long-term difference in ventilation defect percent assessed by ventilation SPECT-CT - healthy [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
   The long-term difference in lung ventilation between healthyCOVID-19+ and healthyCOVID-19- participants
5. Long-term difference in perfusion defect percent assessed by perfusion SPECT-CT - healthy [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
   The long-term difference in lung perfusion between healthyCOVID-19+ and healthyCOVID-19- participants
6. Long-term difference in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - healthy [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
   The long-term difference in lung ventilation/perfusion mismatch between healthyCOVID-19+ and healthyCOVID-19- participants
7. Short-term difference in ventilation defect percent assessed by ventilation SPECT-CT - asthmatic [ Time Frame: ≤4-weeks post COVID-19 recovery (Visit 1) ]
   The short-term difference in lung ventilation between asthmaticCOVID-19+ and asthmaticCOVID-19- participants
8. Short-term difference in perfusion defect percent assessed by perfusion SPECT-CT - asthmatic [ Time Frame: ≤4-weeks post COVID-19 recovery (Visit 1) ]
   The short-term difference in lung perfusion between asthmaticCOVID-19+ and asthmaticCOVID-19- participants
9. Short-term difference in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - asthmatic [ Time Frame: ≤4-weeks post COVID-19 recovery (Visit 1) ]
   The short-term difference in lung ventilation/perfusion mismatch between asthmaticCOVID-19+ and asthmaticCOVID-19- participants
10. Long-term difference in ventilation defect percent assessed by ventilation SPECT-CT - asthmatic [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    The long-term difference in lung ventilation between asthmaticCOVID-19+ and asthmaticCOVID-19- participants
11. Long-term difference in perfusion defect percent assessed by perfusion SPECT-CT - asthmatic [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    The long-term difference in lung perfusion between asthmaticCOVID-19+ and asthmaticCOVID-19- participants
12. Long-term difference in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - asthmatic [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    The long-term difference in lung ventilation/perfusion mismatch between asthmaticCOVID-19+ and asthmaticCOVID-19- participants
13. Longitudinal change in ventilation defect percent assessed by ventilation SPECT-CT - healthy [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    Difference in the 6-month change in lung ventilation between healthyCOVID-19+ and healthyCOVID-19- participants
14. Longitudinal change in perfusion defect percent assessed by perfusion SPECT-CT - healthy [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    Difference in the 6-month change in lung perfusion between healthyCOVID-19+ and healthyCOVID-19- participants
15. Longitudinal change in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - healthy [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    Difference in the 6-month change in lung ventilation/perfusion mismatch between healthyCOVID-19+ and healthyCOVID-19- participants
16. Longitudinal change in ventilation defect percent assessed by ventilation SPECT-CT - asthmatic [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    Difference in the 6-month change in lung ventilation between asthmaticCOVID-19+ and asthmaticCOVID-19- participants.
17. Longitudinal change in perfusion defect percent assessed by perfusion SPECT-CT - asthmatic [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    Difference in the 6-month change in lung perfusion between asthmaticCOVID-19+ and asthmaticCOVID-19- participants.
18. Longitudinal change in ventilation/perfusion mismatch assessed by ventilation/perfusion SPECT-CT - asthmatic [ Time Frame: 6-months post COVID-19 recovery (Visit 2) ]
    Difference in the 6-month change in lung ventilation/perfusion mismatch between asthmaticCOVID-19+ and asthmaticCOVID-19- participants.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

community sample

Criteria

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

Contacts and Locations

Contacts

Contact: Sarah Svenningsen, PhD; +1 (905) 522-1155 ext 37313; svennins@mcmaster.ca

Locations

Canada, Ontario

St. Joseph's Healthcare Hamilton; Recruiting

Hamilton, Ontario, Canada, L8N 4A6

Contact: Sarah Svenningsen, PhD 1 (905) 522-1155 ext 37313 svennins@mcmaster.ca

Sub-Investigator: Manali Mukherjee, PhD

Sub-Investigator: Parameswaran Nair, MD, PhD

Principal Investigator: Sarah Svenningsen, PhD

Sub-Investigator: Christopher Marriott, MD, PhD

Sub-Investigator: Terence Ho, MSc, MD

Sponsors and Collaborators

McMaster University

Research St. Joseph's - Hamilton

Cyclomedica Australia Pty Ltd

Investigators

• Principal Investigator: Sarah Svenningsen, PhD; McMaster University

More Information

• Responsible Party: McMaster University
• ClinicalTrials.gov Identifier: NCT04549636
• Other Study ID Numbers: FIRH002
• First Posted: September 16, 2020
• Last Update Posted: September 10, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: IPD will not be shared with other researchers.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by McMaster University:

covid-19; lung ventilation; lung perfusion; V/Q SPECT; lung health; Technegas

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases