COVID-19 Related Lung Ventilation and Perfusion Injury

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Covid-19; Asthma
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 92

Contacts and Locations

• Study Contact: Name: Sarah Svenningsen, PhD; Phone Number: 37313 +1 (905) 522-1155; Email: svennins@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
      • Contact: Sarah Svenningsen, PhD; Phone Number: 37313 1 (905) 522-1155; Email: 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

community sample

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Research St. Joseph's - Hamilton; Cyclomedica Australia Pty Ltd
• Investigators: Principal Investigator: Sarah Svenningsen, PhD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: August 28, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: covid-19; lung health; lung ventilation; lung perfusion; V/Q SPECT; Technegas
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: FIRH002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No