The Pathophysiology of Swallowing Impairment in People Recovering From COVID-19
Conditions: Covid19
Sponsor: University Health Network, Toronto

The Pathophysiology of Swallowing Impairment in People recovering from COVID-19 Infection      
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UHN Ethics Protocol: 20-5477 
 
 
 
 
 
 
 
Version: Apr 13, 2021  
 
 
 
 
STUDY PROTOCOL 
 
The Pathophysiology of Swallowing Impairment in  
People recovering from COVID-19 Infection 
 
NCT 04537650 
 
PI: Catriona M. Steele, Ph.D. 
 
Swallowing Rehabilitation Research Laboratory 
KITE Research Institute, Toronto Rehabilitation Institute, University Health Network

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TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS ................................................................................................................. 3 
PROTOCOL SUMMARY .................................................................................................................... 4 
1.0 General Information ................................................................................................................. 6 
2.0 Introduction .............................................................................................................................. 7 
3.0 Study Objectives and Hypothesis.............................................................................................. 7 
3. 1 Purpose ................................................................................................................................ 7 
3.2 Objectives .............................................................................................................................. 9 
3.3 Hypothesis ........................................................................................................................... 10 
4.0 Study Design ............................................................................................................................ 10 
Data Collection Procedure ........................................................................................................ 10 
Compensation ........................................................................................................................... 14 
File Transfer .............................................................................................................................. 14 
ClinicalTrials.gov Registration ................................................................................................... 14 
5.0 Selection of Subjects ............................................................................................................... 14 
Participants ............................................................................................................................... 14 
Recruitment .............................................................................................................................. 14 
Inclusion Criteria ....................................................................................................................... 15 
Exclusion Criteria....................................................................................................................... 15 
6.0 Risks and Benefits ................................................................................................................... 15 
Risks .......................................................................................................................................... 15 
Benefits ..................................................................................................................................... 16 
Incidental Findings .................................................................................................................... 16 
7.0 Statistics .................................................................................................................................. 16 
8.0 Data Safety and Monitoring Plan ............................................................................................ 17 
9.0 Data Handling and Record Keeping ........................................................................................ 17 
10.0 Conflicts of interest ............................................................................................................... 18 
11.0 Additional Ethics Reviews ..................................................................................................... 18 
12.0 References ............................................................................................................................ 18 
 
 
 

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LIST OF ABBREVIATIONS 
 
PrC-19  
People recovering from COVID-19 
VFSS 
 
Videofluoroscopic Swallowing Study 
LVC 
 
Laryngeal Vestibule Closure  
 
 

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PROTOCOL SUMMARY 
Full Title 
The Pathophysiology of Swallowing Impairment in People Recovering 
from COVID-19 Infection. 
Short Title 
 
Swallowing impairment after COVID-19. 
Sample Size  
 
N=100 (approximately 25 at each collaborating site and 50 at the 
University Health Network) 
Study Population  
 
Patients who are recovering from COVID-19 infection.  
Accrual Period 
 
October 15, 2020 to January 31, 2022 
Study Design 
 
This is an observational study, in which people recovering from COVID-19 
infection will attend two outpatient clinic visits for a comprehensive 
swallowing assessment. The assessment will include a videofluoroscopy, 
measurement of respiratory-swallow coordination using a digital 
stethoscope, measures of tongue and cough strength and patient 
reported measures that will help us to understand the presence and 
impact of swallowing impairment (dysphagia) in this population. 
Study Duration 
 
October 15, 2020 to January 31, 2022 
Procedure 
Participants will be asked to attend two 60 minute visits where we will 
capture a videofluoroscopy, measurement of respiratory-swallow 
coordination using a digital stethoscope, measures of tongue and cough 
strength and patient reported measures that will help us to understand 
the presence and impact of swallowing impairment (dysphagia) in this 
population. If requested, it may be possible to arrange for both visits to 
take place on the same day. 
Primary Outcomes 
 
 Frequency of boluses (per consistency) on which the participant 
displays unsafe swallows, defined as scores of 3 or higher on the 
Penetration-Aspiration Scale (Rosenbek et al., 1996). 
 Frequency of boluses (per consistency) on which the participant 
displays inefficient swallows, defined as swallows with pharyngeal 
residue measured  to fill 1% or more of an anatomical reference 
scalar [(C2-4)2] on a lateral view x-ray. 
Secondary Outcomes 
 
 Frequency of boluses (per consistency) on which the participant 
displays time-to-laryngeal-vestibule-closure more than 1 standard 
deviation above the healthy reference mean (Steele et al.,2019). 
 Frequency of boluses (per consistency) on which the participant 
displays laryngeal-vestibule-closure duration more than 1 standard 
deviation below the healthy reference mean (Steele et al., 2019). 
 Pixel-based measurement of pharyngeal area at rest from a single 
a lateral view x-ray image, and classified as below or above 1 

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standard deviation from the healthy reference mean (Steele et al., 
2019). 
 Frequency of boluses (per consistency) on which the participant 
displays pharyngeal area above the 75th percentile healthy 
reference value on the frame of maximum constriction (Steele et 
al., 2019). 
 Frequency of boluses (per consistency) on which the participant 
displays multiple swallows, above the 75th percentile healthy 
reference value (Steele et al., 2019). 
Exploratory Outcomes 
 
 Frequency of boluses (per consistency) on which post-swallow 
inspiration is seen immediately following the swallow. 
 Maximum value across 3 repetitions of a maximum tongue-palate 
press task, measured using the Iowa Oral Performance Instrument 
in an anterior position. 
 Range of diet textures included in the participant's diet, measured 
using the International Dysphagia Diet Standardisation Initiative 
Functional Diet Scale. 
 Total and individual question scores on the Sydney Swallow 
Questionnaire.  
 Reported dyspnea using the Modified Medical Research Council 
Dyspnea Scale. 
 Maximum peak voluntary cough flow across 3 repeated coughs 
through a peak-flow meter. 
 Patient report of any changes (Yes/No) they have experienced in 
taste or smell associated with their COVID-19 infection. 
Endpoints of the study 
 
Recruitment and completed data collection in 100 patients across the 3 
study sites. 
 
 
 
 
 
 

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1.0 General Information 
Protocol title: The Pathophysiology of Swallowing Impairment in People Recovering from COVID-19 
Infection. 
 
Study principal investigator:  
Dr. Catriona Steele 
The KITE Research Institute, Toronto Rehabilitation Institute, University Health Network 
550 University Ave, 12th floor 
Toronto, Ontario, Canada 
M5G 2A2 
Tel: 416-597-3422 x 7603 
 
Co-investigators for Toronto region:  
Dr. Azadeh Yadollahi 
The KITE Research Institute, Toronto 
Rehabilitation Institute, University 
Health Network 
550 University Ave, 12th floor 
Toronto, Ontario, Canada 
M5G 2A2 
Tel: 416-597-3422 x 3659 
Dr. Steven Pong 
The KITE Research Institute, Toronto 
Rehabilitation Institute, University 
Health Network 
550 University Ave, 12th floor 
Toronto, Ontario, Canada 
M5G 2A2 
Tel: 416-597-3422 x 7896 
 
Dr. Mark Bayley 
Toronto Rehabilitation Institute, University Health Network 
550 University Ave, 3rd floor 
Toronto, Ontario, Canada 
M5G 2A2 
 
Co-investigator for the Hamilton/Niagara region:  
 
Dr. Ashwini Namasivayam-MacDonald 
McMaster University, Department of Rehabilitation Science 
1400 Main St West, IAHS room 420 
Hamilton, Ontario, Canada 
L8S 1C7 
Tel: 917-676-0772 
 
Co-investigator for the Florida region:  
 
Dr. Emily Plowman 
University of Florida, Department of Speech and Hearing Science 
1396 Center Drive, DG-130 
Gainesville, Florida, United States 
32611 
Tel: 352-273-8632 

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2.0 Introduction 
The recent spread of COVID-19 has led to an international pandemic, with >90 million confirmed cases 
to date worldwide, of which 22.5 million confirmed cases and >375,000 deaths have been reported in 
the USA. Infected individuals commonly experience severe respiratory difficulties and pneumonia, 
leading to hospital admission and the need for intensive care and mechanical ventilation. Emerging 
evidence suggests that impaired taste and smell may be early markers of the disease, and that in 
severe cases, there may be neurological damage in in the medulla, an important brainstem control site 
for both respiration and swallowing (Jean, 2001). Given the overlapping neuroanatomical regulation of 
breathing and swallowing, we hypothesize that dysphagia (swallowing impairment) will be common in 
People recovering from COVID-19 (PrC-19) and associated with poorer outcomes. Dysphagia involves 
impairments of swallowing safety and/or efficiency (Lovato and deFilippis, 2020). Impaired swallowing 
safety involves penetration or aspiration of material into the airway; impaired swallowing efficiency 
involves pharyngeal residue after the swallow, which, in turn, becomes a risk for secondary aspiration 
(Steele et al., 2020). Aspiration is considered a risk for pneumonia (Pikus et al., 2003; Arnold et al., 
2016; Martino et al, 2005), which is a frequent reason for readmission to hospital (Prescott et al., 
2015). 
We will establish 3 regional research clinics that will offer comprehensive swallowing assessments to 
PrC-19 after initial recovery and a confirmed negative test for continuing COVID-19 infection. These 
research clinics will draw on established connections to clinicians in the Toronto area (PI Steele); the 
Hamilton-Niagara region to the west of Toronto (Co-I Namasivayam-MacDonald) and in Gainesville, 
Florida (Co-I Plowman). The assessments will include the collection of case history information, 
videofluoroscopy (i.e., a dynamic swallowing x-ray), use of a novel digital stethoscope to measure 
respiratory-swallow coordination, measures of other risk factors for dysphagia (e.g. bulbar muscle 
strength) and patient-reported outcomes. Detailed analyses of the videofluoroscopy swallowing 
studies (i.e. dynamic x-rays) will identify specific measures of swallowing that fall outside the range of 
normal variation based on comparison to healthy reference values established through our research 
program exploring swallowing physiology on liquids of different consistencies.  
3.0 Study Objectives and Hypothesis 
3. 1 Purpose 
The proposed studies will be an extension of our current work exploring swallowing physiology in 
healthy adults and patients with dysphagia of various etiologies (Amyotrophic Lateral Sclerosis, 
traumatic Spinal Cord Injury, oropharyngeal cancer treated with radiation, Chronic Obstructive 
Pulmonary Disease, and Parkinson Disease). This work has resulted in the development and 
dissemination of a novel, evidenced based and standardized method for the analysis of 
videofluoroscopic swallowing studies (VFSS) known as the ASPEKT Method (Analysis of Swallowing 
Physiology: Events, Kinematics and Timing). Using this method, we have determined and published the 
first comprehensive set of normative reference values for swallowing physiology in a sex-balanced 
sample of healthy adults up to the age of 60 (Steele, Peladeau-Pigeon et al., 2019; Steele Swallowing 
Lab, 2019) across all liquid consistencies of the International Dysphagia Diet Standardisation Initiative 

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framework (Cichero et al., 2017; Cichero et al., 2017). Importantly, this work has afforded clinicians 
and researchers the ability to understand mechanisms of swallowing impairment in their patients, by 
providing a normative reference framework to index and identify specific measures of swallowing that 
fall outside the range of normal variation. We have recently extended this work by completing the 
analysis of a dataset collected in a sex-balanced sample of healthy older adults (> age 60) (in progress), 
which now enables us to account for age related changes when using reference data to identify 
swallowing pathophysiology in older patients.  
Systematic methods for analyzing these data have enabled us to identify abnormalities in swallowing 
that most commonly explain penetration-aspiration and pharyngeal residue. In the proposed study, we 
will use the ASPEKT Method to identify pathophysiological mechanisms of impaired swallowing in PrC-
19. Findings from the proposed study will provide foundational evidence for treatment 
recommendations in PrC-19 with dysphagia. 
In healthy individuals, the swallow is usually positioned partway through an outward breath, such that 
the respiratory pause associated with swallowing is bracketed on either side by expiration (Brodsky et 
al., 2010; Martin-Harris, 2008; Martin-Harris et al., 2005; Butler et al, 2007). This positioning of 
swallowing in the respiratory cycle is considered optimal for airway protection, so that any remaining 
material in the laryngeal vestibule may be expelled by exhalation immediately after the swallow. Post-
swallow inspiration has been observed as an abnormal respiratory-swallow coordination pattern in 
some clinical populations and is thought to represent a risk for aspiration of material into the airway 
(Brodsky et al, 2018; Brodsky et al., 2010; Butler et al, 2007; Martin-Harris et al., 2017). Incorporating 
measurements of respiratory-swallow phasing into clinical swallowing assessments has the potential to 
identify individuals at heightened risk of aspiration.  
Historically, the combined measurement of breathing and swallowing has been a research activity 
using either nasal cannula methods or the measurement of chest wall movements via respiratory 
inductance plethysmography. There is a need for new, portable cost-effective methods that can 
reliably and validly measure respiratory-swallow dynamics during clinical assessment. As an 
exploratory objective, we will address this need with timely implementation of a novel digital 
stethoscope technology. Co-investigators Dr. Pong and Dr. Yadollahi have developed a novel digital 
stethoscope (the “E-Steth”) for use in telehealth community monitoring of cardio-respiratory function 
in PrSC-19. This innovative device uses a microphone mounted inside a stethoscope head to record 
physiological sounds into the Voice-Memo application on a smart phone. The recording can easily be 
sent to a clinician, who can run diagnostic signal processing algorithms. In this study, we will adapt the 
E-Steth technology to identify abnormalities in respiratory-swallow coordination, in the form of 
inspiratory airflow immediately after the swallow. Automatic signal processing algorithms previously 
validated for the measurement of airflow in sleep (Montazeri et al., under review) can be used to 
classify post-swallow airflow direction as expiratory (typical) or inspiratory (abnormal). 
 
 

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3.2 Objectives 
Our objective is to understand the nature of swallowing impairment in PrC19, based on the following 
outcome measures: 
Primary Outcomes: 
 Frequency of boluses (per consistency) on which the participant displays unsafe swallows 
defined as scores of 3 or higher on the Penetration-Aspiration Scale (Rosenbek et al., 1996) 
 Frequency of boluses (per consistency) on which the participant displays inefficient swallows 
defined as swallows with pharyngeal residue measured  to fill 1% or more of an anatomical 
reference scalar [%(C2-4)squared] on a lateral view x-ray (Steele, 2020). 
 
Secondary Outcomes:  
 Frequency of boluses (per consistency) on which the participant displays time-to-laryngeal 
vestibule-closure more than 1 standard deviation above the healthy reference mean (Steele et 
al.,2019) 
 Binary classification of a single pixel-based measure of pharyngeal area at rest, traced from a 
lateral view x-ray, and classified as below or above 1 standard deviation from the healthy 
reference mean (Steele et al., 2019) 
 Frequency of boluses (per consistency) on which the participant displays pharyngeal area above 
the 75th percentile healthy reference value on the frame of maximum constriction (Steele et 
al., 2019) 
 Frequency of boluses (per consistency) on which the participant displays multiple swallows, 
above the 75th percentile healthy reference value (Steele et al., 2019) 
 
Exploratory Outcomes: 
 Frequency of boluses (per consistency) on which post-swallow inspiration is seen immediately 
following the swallow. 
 Maximum value across 3 repetitions of a maximum tongue-palate press using the Iowa Oral 
Performance Instrument in an anterior position. 
 Range of diet textures included in the participant's diet, measured using the International 
Dysphagia Diet Standardisation Initiative Functional Diet Scale 
 Total and individual question scores on the Sydney Swallow Questionnaire 
 Reported dyspnea using the Modified Medical Research Council Dyspnea Scale 
 Maximum peak voluntary cough flow across 3 repeated coughs through a peak-flow meter 
 Patient report of any changes (Yes/No) they have experienced in taste or smell associated with 
their COVID-19 infection 
 
 

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3.3 Hypothesis 
Our current expectations are that PrC-19 will show differences in swallowing function and physiology 
compared to age- and sex-matched reference values (Steele, 2019), as listed in the following table:  
 
 
 
 
 
 
 
 
 
 
 
 
We expect PrC-19 patient to report swallowing-related burden. We hypothesize that post-swallow 
inspiration (a sign of respiratory-swallow discoordination) will be seen more commonly in PrC-19 
compared to healthy reference data (Valenzano et al, 2020), and will be particularly common in those 
who report dyspnea. 
4.0 Study Design  
This is an observational study, in which people recovering from COVID-19 infection will attend two 
outpatient clinic visits for a comprehensive swallowing assessment. The assessment will include a 
videofluoroscopy, measurement of respiratory-swallow coordination using a digital stethoscope, 
measures of tongue and cough strength, and patient-reported measures that will help us to 
understand the presence and impact of swallowing impairment (dysphagia) in this population, as 
compared to reference data from healthy adults that has previously been collected and published by 
our lab. 
Data Collection Procedure 
We expect study participation to involve an initial 30 minute telephone or video conference call to 
review the consent documents, a 60 minute session to capture non-radiographic data, and a 60 minute 
session to capture the radiographic data. If requested, it is possible to arrange for both of the data 
Parameter 
Prediction in PrC-19                                                             
(vs age-matched healthy reference values) 
Penetration-Aspiration 
Higher frequency and more likely to be silent 
Time-to-Laryngeal-
Vestibule-Closure (LVC) 
Later closure due to priority of respiration 
LVC duration 
Shorter due to underlying respiratory challenges 
Pharyngeal Area at Rest 
Larger due to muscle weakness and atrophy.       
Note: reference values show significant sex difference 
with larger area in males. 
Pharyngeal Area at 
Maximum Constriction  
Larger (i.e. poor constriction)                                       
due to muscle weakness and atrophy 
Residue 
Greater due to poor constriction 
# of swallows per bolus 
Higher due to poor bolus clearance 

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collection appointments to take place on the same day, although it is not possible to guarantee back-
to-back scheduling and a delay between the sessions is likely.  
Infection Control and Safety Procedures for the Face to Face Appointments: 
a. We will contact the participant 2 days prior to each study appointment and use the UHN 
COVID 19 screening questions to confirm that they do not have any current symptoms 
of COVID-19 that are not otherwise explained and are suggestive of possible active 
infection.  This will also confirm that they have not, to their knowledge, been exposed to 
someone who has active COVID-19. Two hours prior to each appointment, we will ask 
them to complete the UHN COVID-19 screening app questions on their smart phone (at 
www.UHNScreen.ca), or, to arrive at the facility in time to undergo routine COVID-19 
screening prior to entering the facility. If the participant is accompanied by a 
companion, the companion will also need to complete these routine COVID-19 
screening procedures. Upon arrival, they will be issued with a procedure mask to wear 
at the hospital.  
b. For the initial appointment scheduled in the Swallowing Rehabilitation Research 
Laboratory at Toronto Rehab, the participant and their companion will be met in the 
Elm Street waiting room area at Toronto Rehab and escorted by a study team member 
directly to the 12th floor Swallowing Lab.  
c. For the x-ray appointment at Toronto General Hospital, the participants will be given 
instructions on how to enter the hospital at the Elizabeth Street entrance where COVID-
19 screening is performed, and how to reach the Diagnostic Imaging department, and 
will be met there by a member of the study team.  
d. The study team members present for data collection will follow IPAC rules for limiting 
potential spread of infection. All study team members who will be directly involved in 
data collection are licensed speech-language pathologists who will have been required 
to review the lab’s standard operating procedures relating to infection control and 
safety. They will be required to wear procedure masks at all times and to maintain 2 
meter distancing from the participant and the other team members present, whenever 
possible. Regular disinfection of surfaces in the lab using appropriate wipes will be part 
of the study protocol. For study staff members who will perform tasks that require close 
physical proximity to the participant with less than 2 meters distance, additional 
personal protective equipment (PPE) will be used in accordance with IPAC 
recommendations, including wearing laundered gowns, gloves, face shields, and, if 
appropriate, N95 masks. Regular hand washing and sanitizer use will also be required. 
There will always be a minimum of 2 study team members present, and a buddy system 
will be employed to observe donning and doffing of PPE and to prompt whenever 
necessary to ensure adherence to safe PPE practices. These procedures have been 
reviewed and approved by the KITE Research Restart team. 
 
1. Review of study information and consent form:  
a. All participants who show an interest in participating will be provided with the study 
information and consent form ahead of time. These documents will be sent either by 

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email or by mail, according to the participant’s preference for delivery method. A 
telephone or video-conference call will be scheduled to review these documents and 
answer any questions.  
b. For participants who wish to proceed, we will obtain an initial verbal consent that they 
have understood all the information provided, and, after verifying that they have no 
more questions, we will move forward with scheduling the study appointments. If the 
participant wishes, the study questionnaire can be mailed to them for review in advance 
of their first appointment. However, completion of the questionnaire will not take place 
prior to the first appointment or prior to signing the consent form. 
c. During the first appointment, we will review the study procedures and answer all their 
questions. If they wish to proceed, we will ask them to sign the consent form. A copy of 
the consent form will be provided to the participant.  Data collection will proceed only 
after these steps have been completed. 
 
2. Demographic and medical history information:  
e. Participants will be asked to complete a form capturing demographic, medical history 
and history of COVID-19 management. Those participants who answer yes to questions 
inquiring about current respiratory difficulties (shortness of breath) or swallowing 
difficulties will be asked to complete the section of the questionnaire incorporating the 
Modified Medical Research Council Dyspnea Scale and the Sydney Swallow 
Questionnaire to understand these symptoms in more detail.  For those who report no 
current symptoms of respiratory or swallowing difficulty, this section may be left blank. 
 
3. Non-radiographic data: 
a. Bulbar muscle strength will be measured using 3 repetitions of a maximum effort 
isometric tongue-to-palate press task, measured using the Iowa Oral Performance 
Instrument. The patient will be instructed to “squeeze the bulb as hard as you can 
between your tongue and the roof of your mouth”. A clean, single-use, disposable 
tongue bulb will be used for each participant.  
b. Voluntary peak cough flow will be measured using a Mini-Wright analog peak flow 
meter fitted with a single-use, disposable expiratory one-way valve filter mouthpiece 
following the American Thoracic Society (ATS) standards. The patient will be instructed 
to “cough hard like there is something stuck in your throat” and will perform three 
trials.  
c. Respiratory-swallow coordination data will be collected using the E-Steth digital 
stethoscope during a water swallow screening task. The E-steth stethoscope housing 
will be sanitized with alcohol wipes prior to and after use. The housing itself will not 
come into direct contact with the participant’s neck, because there will be medical 
adhesive tape between the participant’s skin and the device housing. Nevertheless, we 
will use a fresh e-steth device for each participant and will dispose of the device after 
use with each participant. After sanitization, the E-Steth housing will be attached to the 
participant’s neck using double sided tape, over the suprasternal notch. The E-Steth 
output will be connected to a dedicated lab cell phone/MP3, iPad or laptop computer 
running the Voice Memos application and recorded as .m4a files. The participant will be 

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provided with a cup containing 60 ml of chilled bottled water and asked to take a 
comfortable sip and swallow. This procedure will be repeated up to 4 times.  If the 
patient completes all 4 sips in without any overt signs of aspiration, a new cup 
containing 90 ml of water will be provided, and the patient will be asked to drink the 
entire 90ml in a sequential fashion without stopping.  
Stopping rule: If the patient demonstrates obvious signs of aspiration, including 
coughing post-swallow at any point in the water swallow screening task, further water 
screening will be discontinued.  
d. Following completion of the first appointment, the participant will be given instructions 
for their second appointment at the Toronto General Hospital diagnostic imaging 
department for the x-ray component of the study. If requested, it is possible to arrange 
for both of the data collection appointments to take place on the same day, although it 
is not possible to guarantee back-to-back scheduling and a delay between the sessions is 
likely. 
 
4. Radiographic data:  
The standardized videofluoroscopic swallowing study  will be performed in the 
Diagnostic Imaging Department at the Toronto General Hospital.  Swallowing x-ray 
appointments are always scheduled during a Tuesday afternoon time-slot. Upon arrival 
at the Toronto General Hospital entrance, the participant (and any companion) will 
again need to pass through the routine COVID-19 screening procedures before entering 
the building. 
 
The x-ray procedure will involve swallowing 3 boluses each of thin, mildly thick and 
extremely thick barium and 1 consecutive drinking task of thin liquid.   
 
Stimulus preparation: Bracco E-Z-Paque® powdered barium will be prepared in 20% w/v 
concentration with water, and thickened to target consistency using Resource Thicken-
Up™ Clear (a xanthan gum thickener developed by Nestlé Health Science). Target 
consistency will be defined using the International Dysphagia Diet Standardisation 
Initiative definitions and Flow Test. For the Toronto site, all stimuli will be prepared in 
the Swallowing Rehabilitation Research Laboratory not longer than 6 hours prior to 
scheduled use, according to a strict standard operating procedure. Barium stimuli will be 
transported to the radiology suite at Toronto General Hospital, as per routine clinical 
procedures. Similar procedures will be followed at the Hamilton and Florida sites. 
 
Procedure: Three cups of each stimulus will be prepared for the experiment, each 
containing 40 ml and organized in a muffin tray placed in front of the participant. If the 
participant completes all 3 thin sips without any observation of aspiration or serious 
residue, a new cup containing 90 ml of thin liquid will be provided, and the participant 
will be asked to drink the entire 90ml in a sequential fashion without stopping. This is a 
routine clinical method for ruling out swallowing safety concerns in patients who do not 
show concerns on single sip tasks. Single-use plastic teaspoons will be placed in the 
extremely thick cups to facilitate serving. The participant will be asked to take a 

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comfortable sip (or spoonful) from each cup. The cups will be weighed on a digital 
balance at the conclusion of the session to derive estimates of sip volume. The order of 
testing will begin with thin liquids and proceed to mildly thick and then extremely thick 
stimuli. 
 
Recording: The videofluoroscopic swallowing study will be captured in lateral projection 
using pulsed videofluoroscopy at a rate of 30 pulses per second, and recorded on a 
synchronized videocapture system at 30 frames per second. The recording system is a 
secure TIMS Dicom system with password access that is connected to the hospital’s 
network, enabling secure saving of all recordings in a folder on our research server. Any 
identifiers visible on the x-ray image (such as the participant’s MRN number or age) will 
be hidden with black electronic screen scrubbers during the first step of data processing 
and prior to assignment for review.  
Stopping rules: Testing of each consistency will be discontinued after the second 
observation of aspiration or serious residue. The entire protocol will be terminated after 
the 4th observation of aspiration. The sequential thin drinking task will only be 
performed if the participant completes all 3 thin sips without any observation of 
aspiration or serious residue. 
Compensation 
Participants will receive a $50 e-gift card for participating in this study.  
File Transfer 
All data processing will take place at the KITE Research Institute - Toronto Rehabilitation Institute -
University Health Network. Each institution will be required to sign a data transfer agreement prior 
sending any data. We will use secure file transfer procedures to transfer the necessary data from the 
collaborating sites to the Toronto lab.  
ClinicalTrials.gov Registration 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  
5.0 Selection of Subjects 
Participants 
We aim to conduct 100 assessments (approx. 25 per collaborating site involved in the study and 
approx. 50 at University Health Network) over a 14-month period.  
Recruitment 
We will adopt three strategies for recruiting participants to this study: 
1) We have linked to the Ontario COVID-19 Prospective Cohort Study (OnCoP) study being conducted 
by the CANCOV study PIs Drs. Margaret Herridge and Angela Cheung at UHN. The CANCOV study team 
has agreed to notify their participants of the opportunity to participate in our study. They will use our 

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study information sheet and referral form for this purpose. They have also suggested that a Swallowing 
Team Member could attend their weekly clinic and speak directly to CANCOV participants who agree to 
consider the study. 
2) We will work through the members of our clinician advisory group and a wider network of clinicians 
in the cities where data collection is happening to solicit referrals of patients who meet the study 
inclusion criteria. We will ask these clinicians to introduce the study opportunity to patients and 
request permission to complete a referral to the study team for future contact. 
3) We will conduct a broad public advertising campaign through local newspapers, magazines, 
websites, mailings and posters at community centres, seniors’ residences, places of worship, and 
around the university and hospital campuses of the study sites (University of Toronto, University 
Health Network Toronto, McMaster University, Hamilton Health Sciences Centre, University of Florida, 
Shands Medical Centre). 
The clinical research coordinator will respond to all inquiries or referrals regarding potential 
participation, contacting the patient by phone or videoconference using Microsoft Teams to discuss 
the study further, obtain initial verbal consent and schedule the study appointments. A reminder call 
will take place 2 days before the scheduled study appointments. 
Inclusion Criteria  
 Adult (18 years of age or older) 
 Positive (or presumed positive) diagnosis of COVID-19 infection not earlier than March 1, 2020 
 At least 2 weeks post positive diagnosis and medical management of COVID-19 infection 
 Currently free from fever or chills; new onset of cough; worsening of chronic cough; new onset 
of sore throat; new onset of nausea/vomiting, diarrhea, stomach pain; eye pain or 
conjunctivitis; unexplained headaches, fatigue, malaise or muscle aches. Individuals with 
continuing complaints of shortness of breath, difficulty breathing, swallowing difficulty or 
decrease/loss of sense of taste or smell will be included.  
 Adequate comprehension of English (able to understand consent form and follow study 
instructions) 
Exclusion Criteria 
We will accept any participants who meet the inclusion criteria, regardless of prior medical history. As 
indicated under the inclusion criteria, children under the age of 18 years old will not be involved in this 
protocol due to the use of radiation. Additionally, pregnant women will be excluded due to the use of 
radiation. 
6.0 Risks and Benefits 
Risks 
The following risks will be disclosed to all participants prior to obtaining their consent to participate: 

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a) It is possible that participants may dislike the taste or texture of some of the thickened liquid 
stimuli in the study. Participants will be reminded that they are free to discontinue participation 
at any time. 
b) It is possible that participants may experience some fatigue during the data collection sessions. 
Participants will be reminded that they should disclose any fatigue or discomfort to the study 
personnel, and that they are free to discontinue any particular session or to withdraw from the 
study at any time. 
c) Participants will receive exposure to radiation during the videofluoroscopy. Based on our 
previous research, we estimate the total duration of exposure to be < 90 seconds, with an 
associated dose estimate of <0.27 milliSieverts. For comparison, a dose of 0.35mSv is reported 
by Moro and Cazzani (2006) to correspond to a risk of 1 in 39,000 of developing a radiation-
induced stochastic effect from a videofluoroscopy. A study of videofluoroscopy radiation 
exposure in patients who completed an 11-task protocol showed that patients with 
neurological diagnoses received the highest exposure time (Mean: 3.1 minutes, 95% confidence 
interval: 2.9 to 3.2 minutes) (Bonilha et al., 2013). Extrapolating from this calculation to the 10-
task protocol for the proposed study, we estimate that patients who complete the entire 
protocol could receive up to 3 minutes of radiation exposure. We will use a warning bell to alert 
the data collection team to exposure time above this limit, and will terminate the protocol at 
the first opportunity following the bell. 
d) Aspiration (entry of material into the airway) is a possible risk during the videofluoroscopic 
swallowing study that will be performed. This risk is always present for videofluoroscopic 
swallowing studies, which are intended to document the presence and severity of swallowing 
abnormalities, including (but not limited to aspiration). When aspiration is observed, standard 
procedures will be followed for documenting its occurrence. The protocol will be terminated 
immediately after the 4th observation of aspiration. Any participant who experiences aspiration 
will be provided with a “Summary of Research Findings” report that they can share with their 
family doctor. If appropriate, they will be referred to appropriate follow-up services. 
e) Participants may experience skin irritation due to the adhesive patches and medical tape used 
to attach the E-steth sensor to the neck. Individuals who report known skin sensitivity or 
allergies to adhesives will be given the option to decline the E-steth component of the study. 
Benefits 
Participants will benefit by receiving a comprehensive swallowing assessment that may not otherwise 
have been available to them.  
Incidental Findings 
In the unlikely event that the video x-ray reveals an unexpected medical finding, the team will generate 
a report and will facilitate referral to appropriate follow-up services. 
7.0 Statistics 
We will use the ASPEKT Method (Steele et al., 2019) to analyze available recordings of thin liquid, 
mildly thick liquid and extremely thick liquid swallows, and compare values to age matched reference 
data (Steele Swallowing Lab, 2019). Our goal is to develop an understanding of the prevalence of 

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abnormal values in PrC-19 taking comorbidities and other related factors into consideration. These 
potential covariate moderators include demographic factors (sex, age, gender, race, ethnicity), pre-
existing or co-existing medical diagnoses, history of the COVID-19 hospitalization including details of 
any ventilator support required, medical history since discharge (including any occurrences of 
respiratory infection), dyspnea, changes in taste and/or smell associated with the COVID-19 infection, 
bulbar muscle strength, cough strength, and abnormal respiratory-swallow coordination. Additionally, 
the person’s ability to tolerate the full range of diet textures and their swallowing-related quality of life 
may be affected by COVID-19 related swallowing difficulties.  
Assuming 100 participants and 3 boluses per consistency, this will result in a dataset of 300 boluses per 
consistency. Our previous research suggests that swallowing can differ across repeated boluses of the 
same consistency within an individual. It is, therefore, reasonable to calculate statistical power at the 
bolus level. A power calculation in Study Size software suggests that a sample of 138 boluses for a 
given consistency will be needed to detect frequencies of abnormal values higher than those seen in 
the healthy reference sample with odds ratios ≥ 2.00 with 80% power. Therefore, the targeted sample 
size should be sufficient both to detect increased frequencies of abnormal values and to allow the 
bivariate exploration of the impact of single covariate moderators on abnormal value frequency. We 
will not have sufficient data to create a multivariate model exploring the relative impact of different 
moderators; however the findings from this analysis will be sufficient to inform future studies in larger 
cohorts. 
8.0 Data Safety and Monitoring Plan 
A clinician advisory panel comprising 9 speech-language pathologists who work in critical care has been 
established to guide this study. Additionally, 3 physicians have agreed to provide medical advice to the 
study team. The clinician advisory group will meet via video-conference every 4-6 weeks over the 
course of the study. Dr. Teresa Valenzano, PhD, SLP(C), Reg. CASLPO will act as chair. Progress reports 
will be provided for review 1 week ahead of these meetings, and presented to the meeting. These 
reports will document the numbers of participants accrued, preliminary trends in the data and any 
adverse events. After discussion, the principal investigator, co-investigators,  collaborators and study 
coordinators will leave the call, to allow for further in camera discussion. In the event that any 
concerns about study continuation are raised during the in camera session, Dr. Valenzano will report 
these back to the study team. 
9.0 Data Handling and Record Keeping 
Routine practices for ensuring the confidentiality and privacy of all participants will be followed in this 
study. All research personnel at the Toronto Rehabilitation Institute are required to sign a 
confidentiality agreement at the time of hire. Research personnel at McMaster University and the 
University of Florida are similarly bound by a confidentiality agreement outlined by the ethics board at 
their institutions. 
Participants will be assigned a non‐identifying alphanumeric study code, and the master key for this 
code will be retained separately by the lead investigators at each site (Dr. Steele, Dr. Namasivayam-
MacDonald, Dr. Plowman) on a secure, password-protected, encrypted research server. Paper-based 

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documents will be stored securely in a locked filing cabinet under the supervision of the lead 
investigators at each site.  
De-identified hard copy data will be transcribed onto an electronic file and transferred to Dr. Steele’s 
lab at the KITE Research Institute – Toronto Rehabilitation Institute - University Health Network. 
Routine daily back-up of this research server will be performed to protect against data loss. 
All de-identified data will be transferred to Dr. Steele using an encrypted file transfer portal, for 
subsequent analysis. Only the participant’s alphanumeric study code number will appear on the data 
collection sheets and in the data collection files.  
Access to participant information and experimental raw data will be restricted to the study personnel 
named in this application. All records will be destroyed after 10 years under the supervision of Dr. 
Steele, Dr. Plowman and Dr. Namasivayam-MacDonald.  
In the event of inappropriate release of personal health information, further release of information will 
be stopped, any information that can be retrieved will be retrieved, the UHN Privacy Office and REB 
will be notified. If applicable, the REB at McMaster University and the University of Florida IRB will be 
notified. Any recommended further actions will be taken. 
10.0 Conflicts of interest 
Professor Steele, the principal investigator, holds current and prior research contracts with Bracco 
Canada and Nestlé Health Science, who are manufacturers of the barium products and thickening 
agents that will be used in this study. She has also served in an advisory capacity on expert panels for 
Nestlé Health Science. These relationships will be disclosed to participants in the study information 
sheet. All products for use in the study will be purchased. Neither Bracco Canada nor Nestlé Health 
Science will have any role as sponsors of this study. Professor Steele will not receive any financial 
payment, either personally or to the lab, related to the use of Nestlé or Bracco products in this study. 
11.0 Additional Ethics Reviews 
Additional ethics approvals have been separately obtained for other sites involved in this study as 
follows: 
 University of Florida 
 McMaster University 
12.0 References 
 
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Jung S, Sarikaya H: Dysphagia in Acute Stroke: Incidence, Burden and Impact on Clinical Outcome. PLoS 
One 11: e0148424, 2016. 
 
Bonilha HS, Humphries K, Blair J, Hill EG, McGrattan K, Carnes B, Huda W, Martin-Harris B: 

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