Test to Stay in School: COVID-19 Testing Following Exposure in School Communities
Phase: NA
Conditions: Covid19
Sponsor: Duke University

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CLIENT CONFIDENTIAL 
 
 
Test to Stay in School: COVID-19 Testing Following Exposure in School 
Communities 
Phase: N/A – prospective, interventional, cohort study 
 
 
Funding Sponsor: 
The Eunice Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD) 
 
 
Protocol Date: 
30 NOV 2021 
Protocol Version: 
4.0 
NCT Number: 
NCT05052580 
Principal Investigator: 
 
Kanecia O. Zimmerman, MD, MPH 
Associate Professor of Pediatrics 
 
Duke University Medical Center 
Duke Clinical Research Institute 
Durham, NC 27701  
Phone: 919-668-8651  
Fax: 919-668-7063 
E-mail: kanecia.obie@dm.duke.edu 
Investigators: 
Daniel Benjamin, MD, PhD 
Ibukun C. Kalu, MD 
Angelique Boutzoukas, MD 
Melissa Campbell, MD 
Ganga Moorthy, MD 
Zeni Scott, MD 
 
 
 

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STATEMENT OF COMPLIANCE 
This study will be conducted in compliance with the protocol, International Council for 
Harmonisation (ICH) E6 (R2) guideline for Good Clinical Practice (GCP), and the applicable 
regulatory requirements from the United States Code of Federal Regulations (CFR), including 
45 CFR 46 (Human Subjects Protection); 21 CFR 50 (Informed Consent), 21 CFR Part 54 
(Financial Disclosure), and 21 CFR 56 (Institutional Review Board [IRB]); as well as 
international regulatory requirements, if applicable. 
All individuals who are responsible for the conduct, management, or oversight of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
 
 

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STUDY PRINCIPAL INVESTIGATOR 
 
The signature below documents the review and approval of this protocol and the attachments 
(e.g., package inserts), and provides the necessary assurances that this clinical study will be 
conducted according to all stipulations of the protocol, including all statements regarding 
confidentiality and according to local legal and regulatory requirements and to the principles 
outlined in applicable United States (U.S.) and international regulations and ICH guidelines. 
 
 
 
 
 
Principal Investigator Name (Print or Type)  
 
 
 
 
 
 
Study PI Signature 
 
Date 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
Statement of Compliance .............................................................................................................. 2 
Table of Contents .......................................................................................................................... 4 
List of Abbreviations ...................................................................................................................... 6 
Protocol History of Changes ......................................................................................................... 7 
Protocol Synopsis ......................................................................................................................... 8 
1 
Background Information and Rationale ................................................................................ 9 
1.1 
Background Information ........................................................................................... 9 
1.1.1 
COVID-19 and Kindergaten-12th grade school closures ............................... 9 
1.2 
Scientific Rationale ................................................................................................. 10 
1.3 
Potential Benefits ................................................................................................... 10 
1.4 
Known Potential Risks ............................................................................................ 10 
2 
Objectives and Outcome Measures ................................................................................... 12 
3 
Study Design ...................................................................................................................... 13 
3.1 
Overall Design ........................................................................................................ 13 
3.2 
Study Definition of Enrollment ................................................................................ 13 
3.3 
Study Definition of Completion ............................................................................... 13 
4 
Study Population ................................................................................................................ 14 
4.1 
Selection of the Study Population .......................................................................... 14 
4.1.1 
Inclusion Criteria ......................................................................................... 14 
4.1.2 
Exclusion Criteria ........................................................................................ 14 
4.2 
Participant Discontinuation/Withdrawal .................................................................. 14 
4.3 
End of Study ........................................................................................................... 14 
5 
Study Procedures ............................................................................................................... 14 
5.1 
Summary of Evaluations ........................................................................................ 14 
5.2 
Enrollment/Baseline ............................................................................................... 15 
5.3 
Testing Period ........................................................................................................ 16 
5.4 
Follow-Up ............................................................................................................... 16 
6 
Assessment of Safety ........................................................................................................ 16 
7 
Study Termination .............................................................................................................. 17 
8 
Statistical Considerations ................................................................................................... 17 
8.1 
Study Endpoints ..................................................................................................... 17 
8.1.1 
Primary Endpoints ...................................................................................... 17 
8.1.2 
Secondary Endpoints ................................................................................. 17 
8.2 
Analysis Plan .......................................................................................................... 18 
8.2.1 
Primary Analysis ......................................................................................... 18 
8.2.2 
Secondary Analysis .................................................................................... 18 
8.2.3 
Subgroup Analysis ...................................................................................... 19 
8.3 
Sample Size Considerations .................................................................................. 19 
9 
Future Use of Study Records ............................................................................................. 19 
10 
Source Documents and Access to Source Data/Documents ............................................. 19 
11 
Quality Control and Quality Assurance .............................................................................. 20 

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12 
Ethics/Protection of Human Participants ............................................................................ 20 
12.1 
Informed Consent Process ..................................................................................... 20 
12.1.1 Pediatric Assent .......................................................................................... 21 
12.2 
Assent Process ...................................................................................................... 21 
12.3 
Documentation of Permission, Assent, and Consent ............................................. 22 
12.4 
Confidentiality and Privacy ..................................................................................... 22 
13 
Data Handling and Record Keeping ................................................................................... 23 
13.1 
Data Handling ......................................................................................................... 23 
13.2 
Data Management Responsibilities ........................................................................ 23 
13.3 
Data Capture Methods ........................................................................................... 23 
13.4 
Types of Data ......................................................................................................... 23 
13.5 
Study Records Retention ....................................................................................... 23 
13.6 
Protocol Deviations ................................................................................................ 23 
14 
Publication Policy ............................................................................................................... 24 
15 
Literature References ......................................................................................................... 25 

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LIST OF ABBREVIATIONS 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CoC 
Certificate of Confidentiality 
COVID-19 
Coronavirus Disease 2019 
DCC 
Data Coordinating Center 
DCRI 
Duke Clinical Research Institute 
DUHS 
Duke University Health Systems 
EUA 
Emergency Use Authorization 
FDA 
Food and Drug Administration 
FERPA 
Family Education Rights and Privacy Act 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Council for Harmonisation 
IRB 
Institutional Review Board 
NC 
North Carolina 
NCDHHS 
North Carolina Department of Health and Human Services 
NIH 
National Institutes of Health 
PHI 
Protected Health Information 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus -2 
UNC 
University of North Carolina 
U.S. 
United States 
 

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PROTOCOL HISTORY OF CHANGES 
Version 
Date 
Summary of Changes 
v1.0 
17 SEP 2021 
N/A - Original protocol 
v2.0 
1 OCT 2021 
Two screening questions have been added to the 
protocol. These screening questions will be 
administered via the existing REDCap link and will 
allow the study team to determine which 
consent/assent packet to send to potential 
participants. 
v3.0 
27 OCT 2021 
Data management platform was changed to AirTable 
to increase security and ease of use. Option for 
study team to obtain verbal consent was added.  
v4.0 
30 NOV 2021 
Broadened language to allow flexibility in testing 
frequency and time points based on evaluation of 
safety data (e.g. tertiary transmission) and feedback 
from the study safety committee and NCDHHS. 
Updated consent forms to reflect the protocol 
modifications. 

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PROTOCOL SYNOPSIS 
Protocol Title: 
Test to Stay in School: COVID-19 Testing Following Exposure in K-12 School 
Communities 
NCT # 
NCT05052580 
Phase: 
N/A, a prospective, interventional study 
Objectives: 
Primary:  
1. Evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2) transmission following exposure in Kindergarten through 12th grade 
schools. 
Secondary: 
1. Characterize the effect of individual-level mitigation practice (e.g., 
masking) on SARS-CoV-2 spread. 
2. Characterize the effect of exposure setting on SARS-CoV-2 spread. 
3. Describe COVID-19-related school absences for up to 14 days 
following within-school SARS-CoV-2 exposure. 
Study Design: 
Participants in school communities who have been exposed to SARS-CoV-2 
will be tested for COVID-19 on the day after exposure (day 1) and at days 3, 5, 
and 7 following initial known exposure. Data will be reviewed weekly by a study 
safety committee and NCDHHS, and updates to the testing protocol (test 
frequency and test time points) will be made based on analysis of data. 
Mitigation practices including masking, the context of exposure (classroom, 
school bus, after school sporting event, lunch, etc.), and results of COVID-19 
test will be documented. 
Study 
Population: 
School communities 
Number of 
Participants: 
Up to 1,000,000  
Number of Sites: 
Single coordinating site 
Duration of 
Study: 
2 years 

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1 
BACKGROUND INFORMATION AND RATIONALE  
1.1 
Background Information  
1.1.1 COVID-19 and Kindergaten-12th grade school closures 
Widespread Kindergarten through 12th grade school closures are the most important COVID-19-
related threats to child health. Since February 2020, children have accounted for one-tenth of 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases; up to 2.2% and 0.04% 
of pediatric cases have resulted in hospitalization or death, respectively, and as many as 50% of 
cases are asymptomatic.1,2 However, children have been far from spared of the downstream 
effects of this pandemic. In March 2020, most Kindergarten through 12th grade schools 
preemptively closed to in-person education in an attempt to limit viral spread. Most publically-
funded Kindergarten through 12th grade schools across the nation, responsible for educating 
>55 million of the nation’s children, remained closed in the early 2020, citing concerns about 
viral transmission and risks to students and staff. Because public schools play such a vital role 
in the educational, social, and emotional development of young children as well as the delivery 
of vital services such as food and healthcare, it is not surprising that early data show food 
insecurity has doubled; 65% of children 9-13 years are less physically active; 1/6th of children 
have worsened behavioral health; suicidality may be increasing, and physical abuse is more 
severe.3-7 The potential consequences of these findings are deep and far-reaching; children with 
food insecurity are twice as likely to be in fair or poor health, more likely to be hospitalized, and 
more likely as adults to have poor job readiness. Chronic absenteeism in early primary school 
decreases the likelihood of reading at grade level by the third grade and increases the risk of 
drop out by 4 times compared to proficient readers.8 Adults with less than a high school 
education are 2.4 times as likely as high school graduates to rate their health as poor and live 
10 years fewer than those with graduate education. Considering these profound impacts, 
access to in-person education is imperative.  
In North Carolina (NC), schools have been able to show low secondary transmission of SARS-
CoV-2 within school buildings.9 Data in school communities confirms that mitigation strategies 
such as proper masking have been imperative in reducing spread in schools.9-11  
Yet, current policies and procedures requiring quarantine after close contact exposures to limit 
further spread have led to hundreds of thousands of missed school days and have threated the 
school workforce, greatly impeding school operations and the ability of children to appropriately 
learn. In the fourth quarter of 2021 in NC alone, more than 40,000 students and staff were 
required to quarantine as a result of being a close contact of a COVID-19 case (unpublished). 
Fortunately, recent CDC and local guidance have eliminated quarantines for most exposed, 
unvaccinated, asymptomatic children who are wearing a mask and who are in close contact with 
another masked, infected child within the classroom setting. However, many quarantines 
continue to result in unvaccinated adults, children exposed to infected adults, and masked 
exposures occurring outside of the classroom (e.g., athletics or busing). Moreover, schools and 
local governments are steadily lifting mask mandates, even as local community cases rise, 
contributing to exponential increases in quarantines that not only keep children and staff out of 
schools and parents out of work, but have often overwhelmed school resources and the public 
health system.  
To address the issue of quarantines while ensuring that the school and surrounding community 
remain safe from SARS-CoV-2 spread, some locales have begun implementing a “test to stay 
strategy”, whereby a close contact undergoes serial testing over a specified duration of time. 

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The close contact must wear a mask during this time period but is not required to undergo 
quarantine as long as the screening tests remain negative and the contact remains 
asymptomatic. While this strategy is supported by strong scientific premise and initial data are 
promising, the impact of this strategy on quarantine, and secondary and tertiary within-school 
transmission has not been systematically evaluated.  
This study will partner with schools to allow students and staff to remain in school following 
exposure if they continue to test negative for COVID-19 over pre-determined intervals. This 
study aims to collect data to assess the spread of SARS-CoV-2 in school communities with 
varying mitigation strategies to provide data-backed guidelines for mitigation strategies in 
schools. The study team will work with NCDHHS and a safety monitoring team on a weekly 
basis to interpret data, evaluate safety, and design next steps (e.g. testing frequency and 
timing). 
  
1.2 
Scientific Rationale  
This study will evaluate spread of SARS-CoV-2 following known exposure in schools. This 
information will be critical for determining future policies surrounding COVID-19 testing, 
quarantine, and mitigation practices in the Kindergarten through 12th grade school environment. 
Staff and students who participate in this study will provide consent for testing and collection of 
data on demographic factors, symptoms, quarantine, test results, and tertiary spread. The 
existing partnerships with schools established through the ABC Science Collaborative, a 
partnership between Duke and University of North Carolina (UNC) faculty and Kindergarten 
through 12th grade schools in NC, which was formed in the summer of 2020 will be leveraged.  
This study will be conducted across multiple age groups of school-age children and staff, 
multiple educational settings, and multiple different educational cultures to increase the potential 
generalizability of study results. Additionally, this study aims to prospectively collect real-world 
data, which otherwise would be unavailable, to guide evidence-based decision- and 
policymaking surrounding transmission and quarantine.  
1.3 
Potential Benefits 
Participants may benefit from COVID-19 testing, symptom screening, masking and early 
identification of COVID-19. Additionally, individuals may benefit from a broader understanding of 
appropriate mitigation strategies to reduce spread of SARS-CoV-2, reduced need for 
quarantine, and increased school attendance. For the school community, this study will permit 
students and staff to stay in school provided they test negative, minimizing disruption to school 
and home operations. The broader impact that data collection has on advancing the scientific 
understanding of COVID-19 and associated outcomes may benefit others in the future. 
Additionally, this study aims to prospectively collect real-world data, which otherwise would be 
unavailable, to guide evidence-based decision- and policymaking surrounding transmission and 
quarantine.  
1.4 
Known Potential Risks 
Community-level risk(s): For school communities to participate in this protocol, there is a 
potential risk for increased exposure to SARS-CoV-2 from elimination of quarantine; however, 

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frequent testing, symptom screening and requirements for masking in a controlled environment 
are designed to minimize this risk to the community.  
Individual-level risk(s): Risks associated with this study include risks associated with the 
COVID-19 testing procedure, specifically risks associated with lower nasal swab and the 
potential loss of confidentiality. 
- 
Potential Risks of Nasal Swabs: Risks include mild irritation, insignificant local pain, 
and minor bleeding. 
- 
Potential Risk of Loss of Confidentiality: There is a potential risk of loss of 
confidentiality. Every effort will be made to protect the participant’s protected health 
information (PHI) as well as other identifying information, but this cannot be guaranteed.  

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2 
OBJECTIVES AND OUTCOME MEASURES 
 
 
Objective 
Endpoints 
Primary: 
Evaluate severe acute 
respiratory syndrome 
coronavirus 2 (SARS-CoV-
2) transmission following 
exposure in Kindergarten 
through 12th grade 
schools. 
 
Proportion and number of students with 
positive COVID-19 test following known 
exposure. 
 
Proportion and number of staff with positive 
COVID-19 tests following known exposure.  
 
Proportion and number of exposures 
undergoing the test-to-stay protocol that 
result in additional transmission. 
 
Time to test positivity among those exposed 
to SARS-CoV-2 and undergoing the test-to-
stay protocol. 
Secondary #1: 
Characterize the effect of 
individual-level mitigation 
measures (e.g., masking) 
on SARS-CoV-2 spread. 
 
 
Proportion and number of masked students 
with positive COVID-19 test who were 
exposed to SARS-CoV-2 from masked 
versus unmasked individuals.  
 
Proportion and number of masked staff with 
positive COVID-19 test who were exposed 
to SARS-CoV-2 from masked compared to 
unmasked individuals 
 
Proportion and number of unmasked 
students with positive COVID-19 tests who 
were exposed to SARS-CoV-2 from masked 
compared to unmasked individuals 
 
Proportion and number of unmasked staff 
with positive COVID-19 tests who were 
exposed to SARS-CoV-2 from masked 
compared to unmasked individuals 
Secondary #2 
Characterize the effect of 
exposure setting on SARS-
CoV-2 spread. 
 
Proportion and number of students with 
positive COVID-19 test after indoor vs. 
outdoor exposure. 
 
Proportion and number of students with 
positive COVID-19 test after athletic vs. 
classroom exposure. 
 
Proportion and number of students with 
positive COVID-19 test after bus vs. 
classroom exposure. 
Secondary #3:  
Describe COVID-19-related 
school absences for up to 
 
Total number of school days missed due to 
symptoms after exposure. 

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14 days following SARS-
CoV-2 exposure. 
 
Total number of school days missed due to 
isolation after positive COVID-19 test. 
 
Total number of school days missed due to 
quarantine after SARS-CoV-2 exposure.  
3 
STUDY DESIGN 
3.1 
Overall Design 
Study design: This is a prospective, interventional study with a primary objective of evaluating 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission following 
exposure in Kindergarten through 12th grade school students and staff. Participants will be 
tested with a COVID-19 testing kit that is Food and Drug Administration (FDA)-authorized under 
an emergency use authorization (EUA) for non-prescription use for both symptomatic and 
asymptomatic evaluation in children and adults. During the initial phase of this study, 
participants who consent to participate in this study will be tested at days 1, 3, 5, and 7 following 
a known COVID-19 exposure on day 0. If a participant does not know of the exposure until more 
than one day following the exposure, they will be tested on the day they become aware of the 
exposure and then resume the aforementioned testing schedule (e.g. participant identifies 
exposure 3 days after the exposure, test on day 3, day 5, and day 7). After the initial phase, the 
number of tests may be reduced and the test time points may change based on analysis of 
current data. All modifications will be made only if deemed safe by the safety monitoring 
committee and NCDHHS. 
If the COVID-19 tests are negative, the participant will remain in the school environment. A 
positive COVID-19 test or the development of symptoms on any day after exposure would 
require isolation according to school, local and state guidelines. Demographic information, daily 
presence or absence of symptoms, whether the infected person or close contact was masked, 
setting of the exposure, test results, and school absences will be collected following consent. 
Data regarding school level mitigation practices will also be collected. Data collected from this 
study may be combined with school-provided data and publicly available community data. 
3.2 
Study Definition of Enrollment 
Study enrollment is defined as the participant has provided informed consent (or assent) and 
completed at least one day of testing in an effort to avoid quarantine.  
3.3 
Study Definition of Completion 
An individual will complete the study after completing all testing days and symptom monitoring 
(up to 14 days), or data entry that explains why all testing was not completed (e.g., positive test, 
symptoms, quarantine).  
 
 

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4 
STUDY POPULATION 
4.1 
Selection of the Study Population 
4.1.1 Inclusion Criteria 
1. Consent completed 
2. Child or adult that is part of a school community 
3. Known exposure to SARS-CoV-2  
4.1.2 Exclusion Criteria 
There are no exclusion criteria for this study, all inclusion criteria must be met for participation. 
Some restrictions to inclusion may apply based on school-specific policies (e.g., optional 
masking). 
4.2 
Participant Discontinuation/Withdrawal 
A participant or his/her parent (or legal guardian) may voluntarily withdraw consent to participate 
in the study at any time. Participants are not obligated to state the reason for withdrawal. No 
additional study data will be collected after consent has been withdrawn, however, all data 
collected prior to consent withdrawal will be maintained in the database.  
4.3 
End of Study 
Participants will be considered off study at the end of the school semester in which they enrolled 
onto the study. 
 
5 
STUDY PROCEDURES 
5.1 
Summary of Evaluations 
Enrollment/Baseline Testing Period 
Follow-Up 
PROCEDURE 
Day 0 
Day 1, 3, 5, 7 
Up to Day 14 
Screening 
X 
 
 
Informed consent/assent 
X 
 
 
Confirm eligibility criteria 
X 
 
 
Demographics 
X 
 
 
Mitigation data collection 
X 
 
 
Exposure information 
X 
 
 

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COVID-19 testing and results 
collection  
 
X 
 
Symptom data 
 
X 
X 
Safety Assessment 
 
X 
 
5.2 
Screening Questions 
Several screening questions will be asked via REDCap prior to consent to assure the correct 
consent is assigned to the person completing the form (e.g. parent/adult consent, or 
consent/assent combination). These screening questions ask about language preference (e.g. 
English or Spanish), and the age of the person who had a within-school COVID-19 exposure 
(e.g. less than 7 years of age, between 7 and 17 years of age, and 18 years of age or older). No 
identifiable information will be collected until after informed consent has been obtained. These 
questions will be used for screening purposes only. 
5.3 
Enrollment/Baseline 
Participants or their parent/legal guardian will provide informed consent (or assent). Applicable 
informed consent from the participant or parent/legal guardian (and assent if applicable) for all 
participants will be documented. After consent, the participant will be assigned a unique ID by 
the school nurse or administrator. The school nurse or administrator will collect study-related 
variables via a spreadsheet using one of two different methods. The school nurse may use 
AirTable, a system designed by Technology and Data Solutions, or standard excel 
spreadsheets, which will be sent to the research team. The research team will have access to 
individual-level data but will not have access to names or other identifiers. While the study team 
will have access to the consents completed via REDCap, the team will not know which unique 
ID belongs to which individual. 
The following information will be collected from the student at the time of enrollment.  
Information may be collected directly from the participant, their parent/legal guardian, or via a 
school nurse. The information will include the following: 
 
Participant demographics (age, sex, English proficiency, and vaccination status) 
 
Mitigation data collection including whether the participant was masked or unmasked, 
and vaccination status (if known) 
 
Exposure details include when exposure occurred, where it occurred, and if the 
individual who caused the exposure was masked or unmasked 

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5.4 
Testing Period 
Eligible participants will undergo COVID-19 testing on days 1, 3, 5, and 7 following known 
SARS-CoV-2 exposure. If a participant is not aware of the exposure until after the day of 
exposure, testing will begin immediately on the day of exposure awareness and then resume 
according to the study schedule (see Table 1 below for examples). Testing will occur at home or 
at school according to the Instructions for Use. Participants will be asked to report symptoms for 
during the testing period. Safety and testing results will also be collected. Pending approval from 
NCDHHS, the number of tests and the test time points may be changed if deemed safe based 
on analysis of prior data. For example, if these stakeholders agree that the Test to Stay protocol 
is safe with two tests rather than four, this change in test frequency may be made. When 
designing this protocol, the study team used a very conservative approach to prevent undue 
harm to participants. Over the next several weeks and months, the study team will work closely 
with stakeholders to modify the test time points and total tests performed to identify the optimal 
testing protocol which is sustainable for schools (time, resources) but also deemed to be safe. 
Table 1. Testing Schedule based on knowledge of exposure  
Exposure day 
Knowledge of exposure day 
Testing days 
0 
0 
1, 3, 5, 7 
0 
1 
1, 3, 5, 7 
0 
2 
2, 3, 5, 7 
0 
3 
3, 5, 7 
0 
4 
4, 5, 7 
0 
5 
5, 7 
5.5 
Follow-Up 
Participants will be asked to report symptoms for up to 14 days following SARS-CoV-2 
exposure. Schools will be asked to report tertiary spread and number of close contacts for 
individuals who tested positive. 
6 
ASSESSMENT OF SAFETY 
Participants will be asked to self-report safety events related to testing and after each testing 
event on pre-specified testing days. Because these tests have undergone rigorous safety 
assessments, this study will only collect safety events related to known testing procedures risks, 
which include nose irritation, local pain around nose, and nose bleeding. Serious and 
unanticipated safety events are not expected to occur in this study and therefore no expedited 
safety reporting will occur. Participants will be provided with contact information if they 
experience any concerning safety events and wish to report them outside of the study safety 
assessment survey. The study principal investigator will review aggregate safety information 
and determine if any of the safety information requires Institutional Review Board (IRB) 
submission and review according to Duke University Health System (DUHS) IRB reporting 
policies.  

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7 
Study Termination 
This study may be terminated at any time by the funding agency or the study principal 
investigators. Reasons for termination may include but are not limited to, if in their judgment, 
there are no further benefits to be achieved from the study. If the study is terminated, 
notifications will be made to the IRB of record and study participants, in accordance with all 
applicable regulations governing the study and site/investigator. 
8 
STATISTICAL CONSIDERATIONS 
8.1 
Study Endpoints 
8.1.1 Primary Endpoints 
Primary Objective: Evaluate severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2) transmission following exposure in Kindergarten through 12th grade schools. 
Primary Endpoints:  
 Proportion and number of students with positive COVID-19 test following known 
within-school exposure. 
 Proportion and number of staff with positive COVID-19 tests following known 
within-school exposure.  
 Proportion and number of exposures undergoing the test-to-stay protocol that 
result in additional (tertiary) transmission. 
 Time to test positivity among those exposed to SARS-CoV-2 and undergoing the 
test-to-stay protocol. 
8.1.2 Secondary Endpoints 
Secondary Objective #1:  Characterize the effect of individual-level masking on SARS-
CoV-2 spread. 
Secondary #1 Endpoints: 
 Proportion and number of masked students with positive COVID-19 test who 
were exposed to SARS-CoV-2 from masked versus unmasked individuals.  
 Proportion and number of masked staff with positive COVID-19 test who were 
exposed to SARS-CoV-2 from masked compared to unmasked individuals 
 Proportion and number of unmasked students with positive COVID-19 tests who 
were exposed to SARS-CoV-2 from masked compared to unmasked individuals 
 Proportion and number of unmasked staff with positive COVID-19 tests who were 
exposed to SARS-CoV-2 from masked compared to unmasked individuals 
Secondary Objective #2: Characterize the effect of exposure setting on SARS-CoV-2 
spread. 
Secondary #2 Endpoints:  

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 Proportion and number of students with positive COVID-19 test after indoor vs. 
outdoor exposure. 
 Proportion and number of students with positive COVID-19 test after athletic vs. 
classroom exposure. 
 Proportion and number of students with positive COVID-19 test after bus vs. 
classroom exposure. 
Secondary Objective #3: Describe COVID-19-related school absences for up to 14 days 
following within-school SARS-CoV-2 exposure. 
Secondary #3 Endpoints: 
 Total number of school days missed due to symptoms after exposure. 
 Total number of school days missed due to isolation after positive COVID-19 
test. 
 Total number of school days missed due to quarantine after SARS-CoV-2 
exposure. 
8.2 
Analysis Plan 
Summary statistics of the schools and the students/staff will be presented using data 
collected during study enrollment. Means/medians with standard deviations (and 
interquartile ranges) will be tabulated.  
8.2.1 Primary Analysis 
For the primary endpoint the proportion of students/staff with positive COVID-19 test will 
be reported and the trend by week will be presented in graphical form. To account for 
the within-school correlation of outcomes, 95% confidence intervals will be estimated for 
the proportion using a generalized estimating equations approach using a working 
independence correlation structure.12  
8.2.2 Secondary Analysis 
The proportion and number of students/staff who reported masking and unmasking will 
be reported and presented in graphical form. The primary analysis will be repeated for 
masked and unmasked participants (students and staff) separately. The primary analysis 
will be repeated for masked and unmasked source of exposure separately.   
School absences will be analyzed by absences due to symptoms, positive COVID-19 
test, or due to quarantine for exposure to SARS-CoV-2. To account for the within-school 
correlation of outcomes, analyses will be conducted using a generalized estimating 
equations approach using a loglink suitable for count outcomes, with a working 
independence correlation structure.  

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To account for within-school correlation, a risk between the schools using a generalized 
estimating equation approach with an identity link and a working independence 
correlation structure will be estimated. The risk difference will be estimated for each 
semester during the study period, as well as overall. Students will be censored by end of 
data or study withdrawal. Censoring will be addressed by incorporating inverse-
probability censoring weights into the regression model, with censoring risk estimated 
with a Kaplan-Meier estimator.  
8.2.3 Subgroup Analysis 
Exploratory subgroup analysis may occur from the information collected as part of this 
study.  
8.3 
Sample Size Considerations 
No formal sample size calculation was completed for this study. This study will enroll up to 
1,000,000 participants. 
9 
Future Use of Study Records  
The research data collected in this study, and provided to the sponsor, will be kept indefinitely.  
Information about this study, including study results, will be published without further permission 
from the participant as detailed in the informed consent form. Participants will not be identified in 
any publications or presentations made about the study.  
After the study is completed, information about the study, including study data, may be 
provided to the National Institutes of Health (NIH). Identifiable data will be kept at the DCRI 
and the DCRI will not share these data with the NIH. With NIH approval, the data submitted 
may be used by other researchers for future research. The study data submitted will be de-
identified, meaning it will not include any information that can identify the participant. The 
study team may also share the de-identified study data with other researchers. When the 
participant’s de-identified study data are provided to other researchers for the purposes of 
future research, it will be done without obtaining additional permission.  
10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS  
Data collected for this study will include data provided from schools, data collected by school 
nurses and administrators, data entered by the participant and/or their parent/guardian directly 
into the Data Coordinating Center (DCC)-held database or into REDCap, and data entered into 
the DCC-held database or REDCap by the study team. All data received from schools will be 
de-identified, aggregate data and be provided in accordance with the Family Education Rights 
and Privacy Act (FERPA) regulations.  
While the study team currently receives data spreadsheets from school nurses and 
administrators via Duke Box, the team will slowly transition to AirTable, which will increase 
security while decreasing school-level burden. Each approved school nurse or administrator will 
be issued their own username. Only authorized users will have access. An AirTable instance 

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will be built for each district such that only individuals from the specific district will have access. 
Data will be entered in real-time, reducing the potential for errors and burden of downloading 
and uploading spreadsheets to Duke Box. Unique IDs will be used rather than participant 
names.  
11 
QUALITY CONTROL AND QUALITY ASSURANCE  
The principal investigator will ensure that all study personnel are appropriately trained and 
applicable documentation is maintained. The DCC will implement quality control procedures 
beginning with the data entry system and generate data quality control checks that will be run 
on the database.  
12 
ETHICS/PROTECTION OF HUMAN PARTICIPANTS  
12.1 Informed Consent Process 
Informed consent and assent procedures are initiated prior to the individual agreeing to 
participate in the study and continuing throughout the individual’s study participation. For this 
study, participants will be consented once per semester, following their initial SARS-CoV-2 
exposure for that semester. Risks and possible benefits of participation in this study will be 
provided to the participants and their parents/guardians, as appropriate, prior to consenting via 
REDCap. The school nurse or administrator will be responsible for providing the REDCap link to 
parents and staff for consent; however, the school nurse will not be involved in the consent 
process. The Duke study team will be available to discuss the study and answer questions. 
In situations where access to internet is limited, and eConsent is a barrier, the study team will 
administer verbal consent. In accordance with the Duke Learning Management System (LMS) 
training titled, “Informed Consent Process and Procedures for Clinical Research” and the 
“Requirements of Study Personnel Conducting the Consent Process” document (last updated: 
9/28/2021), the person obtaining verbal consent will meet the following requirements: 
 
Has completed all training required for individuals conducting research with humans 
(e.g. CITI, HIPAA, and RCR training)  
 
Has completed all consent-specific training involving the consent process at Duke (e.g. 
the training referenced above) 
 
Possesses sufficient knowledge of study, as determined by PI, to be able to adequately 
address questions from a potential participant 
 
Is listed as Key Personnel for the study and identified on Delegation of Authority log by 
PI as having authority to consent participants   
 
Has prior experience or plans to be observed for at least the first two 
consents                              
Per the LMS training and the document cited above, “The most appropriate individuals for this 
role on the study include the PI, co-PI, clinical research coordinator, clinical research nurse 
coordinator, and regulatory coordinator; however, this does not preclude others on the study 
team from assuming this role provided the criteria are met.” Ultimately, the PI will make the 
determination on who is eligible to obtain informed consent. For individuals who do not possess 
prior experience, the PI will implement a plan by which the individual is observed conducting 

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consent at least the first two times by an individual experienced in the process (“Observer”), and 
the Observer will provide immediate feedback, including corrective actions. Documentation of 
successful completion of informed consent observation will be maintained in accordance with 
individual CRU policies, e.g., personnel files, study regulatory binder, etc. 
This study enrolls children. Per 21 CFR 50.3 (o) and 45CFR 46.402 (a) “children” is defined as 
persons who have not attained the legal age for consent to treatments or procedures involved in 
clinical investigations (or the research), under the applicable law of the jurisdiction in which the 
clinical investigation (or the research) will be conducted and so the legal age for consent may be 
different in different jurisdictions.  
Consent forms with detailed descriptions of the study procedures, risks, and potential benefits 
will be approved by the IRB. Consent forms (and assent forms, if appropriate) will be provided to 
the participant or the participant’s parent/guardian electronically to read and note any questions.  
The consent must be completed prior to performing any study-specific procedures. 
If information about new potential risks related to participating in this study emerges or 
procedures are modified, the consent/assent forms will be updated to reflect those potential 
risks, and the participants currently active in the study will be re-consented with the updated 
consents. If the consent forms are changed for any other reason and the local IRB requires re-
consenting of active participants, the participant will be asked to review and complete the new 
consent forms electronically. 
A copy of the executed informed consent/assent documents will be provided to the participant 
and/or the participant’s parent/legal guardian (as appropriate) for their records.  
The assent process for the study will occur as appropriate, as described, per protocol. 
12.1.1 Pediatric Assent 
The participant should be informed about the study to the extent compatible with the 
participant’s understanding. As required by local regulatory authorities, the participant should 
assent to participate in the study. A separate IRB--approved assent form, describing (in 
simplified terms) the details of the study, study procedures, and risks, may be used. Assent 
forms do not substitute for the consent form signed by the participant’s parent or legal guardian.  
Under 21 CFR 50.52, and 50.55, and 45 CFR Part 46.405, the IRB of record is responsible for 
determining that adequate provisions are made for soliciting the assent of children.  
12.2 Assent Process  
This study includes minor participants who may be enrolled in the study only with the consent of 
their parent/legal guardian. The minor participant will be informed about this study to the extent 
compatible with his/her neurodevelopmental abilities. Participants who are nonverbal or 
minimally verbal, have significant intellectual disability, are younger than seven years old, or 
have marked thought disorganization or positive psychotic symptoms are very unlikely to be 
considered developmentally able to provide assent. If the participant is developmentally able to 
understand the concepts of voluntary participation in research, the participant will be given a 
simplified, developmentally appropriate assent form to review and will be asked to sign and 
personally date the assent form. Electronic consent will be obtained via REDCap. 

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Assent does not substitute for the permission form signed by the participant’s parent/legal 
guardian.  
12.3 Documentation of Permission, Assent, and Consent 
Permission, assent, and consent must be documented using forms and processes determined 
by the DUHS IRB.   
Prior to enrollment of participants into this study, the protocol, the applicable informed 
consent/assent template, and any materials or advertisements presented to participants will be 
reviewed and approved by the DUHS IRB.  
Should amendments to the protocol and consent/assent documents be required, the 
amendments will be written by the sponsor and approved by the DUHS IRB. 
For non-English speakers, a fully translated consent may be used to obtain informed consent. 
The fully translated consent must be approved by the DUHS IRB and executed according to 
local requirements.  
The informed consent process will be conducted and the form fully executed, before the 
participant undergoes any study-specific procedures. 
12.4 Confidentiality and Privacy 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s) and their agents. Therefore, the study protocol, documentation, 
data, and all other information generated will be held in strict confidence. No information 
concerning the study or the data will be released to any unauthorized third party without prior 
written approval of the sponsor. Participants will provide information in the nurse's office or in a 
private space, adhering to school policies. This will vary from school to school but will follow 
each school's regular policies and procedures. This will occur during the school either before, 
during or after the day, when the participant learns that they have had an exposure. The 
information provided by participants will strictly relate to their COVID-19 exposure and testing. 
The principal investigator will ensure that the use and disclosure of PHI obtained during a 
research study complies with the Health Insurance Portability and Accountability Act (HIPAA) 
Privacy Rule. The rule provides U.S. federal protection for the privacy of PHI by implementing 
standards to protect and guard against the misuse of individually identifiable health information 
of participants participating in clinical trials. Authorization is required from each research 
participant (i.e., specific permission granted by an individual to a covered entity for the use or 
disclosure of an individual’s protected health information). A valid authorization must meet the 
implementation specifications under the HIPAA Privacy Rule. Authorization may be combined in 
the informed consent document (if approved by the IRB). 
The study participant’s contact information will be securely stored for use during the study. At 
the end of the study, all records will continue to be kept in a secure location for as long a period 
as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the DCC. All study data systems used by the DCC 
research staff will be secured and password protected.  

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To further protect the privacy of study participants, this study is covered by a Certificate of 
Confidentiality (CoC) from the NIH. The CoC limits the ability of courts and other agencies from 
forcing the study team to share participant information or body fluids during a legal or legislative 
action without the participant’s permission. The CoC does not restrict the parents from sharing 
information voluntarily. 
13 
DATA HANDLING AND RECORD KEEPING 
The investigator is obligated to conduct this study in accordance with U.S. Federal Regulation 
21 CFR 312.60-68 as specified by applicable state and federal laws, and the International 
Council for Harmonisation: Good Clinical Practice: Consolidation Guideline.  
13.1 Data Handling 
Data will be captured using multiple systems and approaches. All data collected in the context 
of this study will be stored and evaluated per applicable regulatory requirements and guidance 
for electronic records.  
Data will be stored and evaluated in a manner that protects participant confidentiality in 
accordance with the legal stipulations applying to confidentiality of data. 
13.2 Data Management Responsibilities 
The DCC for this study will be responsible for data management, quality review, analysis, and 
reporting of the study data. 
13.3 Data Capture Methods 
School personnel will collect a subset of the study-required data. This data will be provided to 
the DCC via spreadsheets with patient identification numbers or through AirTable. The school 
will hold the key to connect the participant identification numbers to the participant names and 
this key will not be shared with the PI or any of the DCC study team. 
Participant/parent/guardian-reported data will be entered directly into the DCC-held database or 
the Duke REDCap system.  
13.4 Types of Data 
Data for this study will include participant reported information including demographics, 
mitigation practices, exposure information, safety, and COVID-19 test results. Additional de-
identified data may be provided by schools, including demographics and school attendance; 
these data will be provided in aggregate or at the individual level.  
13.5 Study Records Retention 
All records will be retained for at least 6 years after study completion, per Duke Policy. 
13.6 Protocol Deviations 
A protocol deviation is any noncompliance/unplanned excursion from approved investigational 
plan (e.g., protocol), or ICH GCP guidelines. The noncompliance may be on the part of the 

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participant, investigator, or staff. No protocol deviations will be reported for this study, but 
indirectly tracked via missing data in the database.  
14 
PUBLICATION POLICY  
The study will adhere to authorship standards described in the International Committee of 
Medical Journal Editors’ Recommendations for the Conduct, Reporting, Editing, and Publication 
of Scholarly Work in Medical Journals. Authorship credit should be based on: 
• 
Substantial contributions to conception and design, acquisition of data, or 
analysis and interpretation of data 
• 
Drafting the article or revising it critically for important intellectual content 
• 
Final approval of the version to be published 
• 
Agreement to be accountable for all aspects of the work in ensuring that 
questions related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved 
Additional authorship requirements imposed by individual journals will also be met. Authorship 
credit will be assigned in an equitable fashion and will be commensurate with participation and 
effort on the individual manuscript. Committee members will appear as authors on manuscripts 
based solely on actual contributions to the writing of the manuscript. 
All investigators funded by the NIH must submit or have submitted for them to the National 
Library of Medicine’s PubMed Central an electronic version of their final, peer-reviewed 
manuscripts upon acceptance for publication, to be made publicly available no later than 12 
months after the official date of publication. The NIH Public Access Policy ensures the public 
has access to the published results of NIH-funded research. It requires investigators to submit 
final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. Further, the policy stipulates that these papers must be 
accessible to the public on PubMed Central no later than 12 months after publication.  
Refer to: 
http://publicaccess.nih.gov/  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html 

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15 
LITERATURE REFERENCES 
1. 
Pediatrics AAo, Association CsH. Children and COVID-19: State Data Report. In. 
Online2021. 
2. 
Poline J, Gaschignard J, Leblanc C, et al. Systematic Severe Acute Respiratory 
Syndrome Coronavirus 2 Screening at Hospital Admission in Children: A French 
Prospective Multicenter Study. Clinical Infectious Diseases. 2020. 
3. 
Bitler MP, Hoynes HW, Schanzenbach DW. The social safety net in the wake of COVID-
19. In. Brookings Papers on Economic Activity2020. 
4. 
Dunton GF, Do B, Wang SD. Early effects of the COVID-19 pandemic on physical 
activity and sedentary behavior in children living in the U.S. BMC Public Health. 
2020;20(1):1351. 
5. 
Patrick SW, Henkhaus LE, Zickafoose JS, et al. Well-being of Parents and Children 
During the COVID-19 Pandemic: A National Survey. Pediatrics. 
2020;146(4):e2020016824. 
6. 
Hill RM, Rufino K, Kurian S, Saxena J, Saxena K, Williams L. Suicide Ideation and 
Attempts in a Pediatric Emergency Department Before and During COVID-19. 
Pediatrics. 2021;147(3):e2020029280. 
7. 
Sidpra J, Abomeli D, Hameed B, Baker J, Mankad K. Rise in the incidence of abusive 
head trauma during the COVID-19 pandemic. Archives of Disease in Childhood. 
2021;106(3):e14-e14. 
8. 
Jacob BA, Lovett K. Chronic absenteeism: An old problem in search of new answers. 
Brookings. 2017. 
9. 
Zimmerman KO, Akinboyo IC, Brookhart MA, et al. Incidence and Secondary 
Transmission of SARS-CoV-2 Infections in Schools. Pediatrics. 2021:e2020048090. 
10. 
Falk A, Benda A, Falk P, Steffen S, Wallace Z, Høeg T. COVID-19 Cases and 
Transmission in 17 K–12 Schools — Wood County, Wisconsin, August 31–November 
29, 2020. MMWR Morb Mortal Wkly Rep 2021. (70):136–140. 
11. 
Gettings J, Czarnik M, Morris E, al. e. Mask Use and Ventilation Improvements to 
Reduce COVID-19 Incidence in Elementary Schools — Georgia, November 16–
December 11, 2020. MMWR Morb Mortal Wkly Rep 2021. (70):779–784. 
12. 
Zeger SL, Liang K-Y, Albert PS. Models for Longitudinal Data: A Generalized Estimating 
Equation Approach. Biometrics. 1988;44(4):1049-1060.