Rapid SARS-CoV-2 IgG Antibody Testing in High Risk Healthcare Workers and Candidacy for Convalescent Plasma Therapy/Prophylaxis
Phase: NA
Conditions: SARS-CoV-2
Sponsor: Indiana University

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
1 
 
 
 
Rapid SARS-CoV-2 IgG Antibody Testing in high risk healthcare workers and candidacy 
for convalescent plasma therapy/prophylaxis 
 
Protocol Number: 
PICU-IUSCC-0736 
 
 
Principal Investigator: 
Courtney M. Rowan, MD 
Assistant Professor, Department of Pediatrics  
Indiana University School of Medicine 
Phone: 317-944-7065 
E-mail: coujohns@iu.edu 
 
Co-Investigators: 
Sophie Paczesny, MD, PhD 
Emery Christopher, MD 
 
 
Statistician:  
 
Hao Liu, PhD 
 
 
Protocol Version: 
March 26, 2020

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
2 
Table of Contents 
 
 
 
BACKGROUND & RATIONALE ............................................................................................................ 3 
 
OBJECTIVES ....................................................................................................................................... 4 
 
STUDY DesigN ................................................................................................................................... 4 
 
ELIGIBILITY CRITERIA ......................................................................................................................... 4 
 
SUBJECT REGISTRATION .................................................................................................................... 5 
 
STUDY PROCEDURES ......................................................................................................................... 5 
 
COLLECTION OF DATA ....................................................................................................................... 7 
 
DATA FORMS AND SUBMISSION SCHEDULE ..................................................................................... 7 
 
POTENTIAL RISKS AND PROCEDURES FOR MINIMIZING RISKS ......................................................... 7 
 
STATISTICAL CONSIDERATIONS ......................................................................................................... 7 
 
Data And Safety monitoring Plan ...................................................................................................... 8 
 
PATIENT CONSENT AND PEER JUDGMENT ....................................................................................... 8 
 
CRITERIA FOR REMOVAL FROM STUDY ............................................................................................ 8 
Appendix I: Recruitment Email ................................................................................................................... 10 
APpendix II: SARS-CoV-2 IgG Antibody Detection Kit Instructions ............................................................. 11 
 
 
 
 
 
 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
3 
  BACKGROUND & RATIONALE 
 
The success of Singapore, Taiwan and Hong Kong in limiting the impact of the sudden acute respiratory 
syndrome coronavirus-2 (SARS-CoV-2), also know as COVID-19, has been attributed to their preparedness 
but mostly to the implementation and distribution of SARS-CoV-2 fast diagnostic tests and establishment 
of decentralized point-of-care (POC) testing (https://www.nature.com/articles/d41587-020-00010-2). So 
far, the frontline response to the SARS-CoV-2 outbreak has been polymerase chain reaction (PCR) testing. 
PCR is the gold standard for diagnosing an infectious agent, and it has the advantage that the primers 
needed for such tests can be produced with relative speed as soon as the viral sequence is known.  
 
The first quantitative reverse-transcriptase-based PCR (RT-PCR) tests for detecting SARS-CoV2 were 
designed and distributed in January by the World Health Organization (WHO), soon after the virus was 
identified. The test protocol is complex and expensive, however, and is mainly suited to large, centralized 
diagnostic laboratories. Tests typically take 4–6 hours to complete, but the logistical requirement to ship 
clinical samples means the turnaround time is 24 hours at best. A new fast PCR test (45 min) from Cepheid 
has been approved by the U.S. Food and Drug Administration on March 21st with availability at the end 
of the month. Rapid POC tests are also needed to accelerate clinical decision-making and to take some of 
the workload off centralized test laboratories. Most importantly, the current state of the matter in Indiana 
University Health system, as well as many around the country is that healthcare workers including from 
the ER and ICU are currently unable to receive adequate testing through existing facilities. Worst, their 
access to appropriate personal protective equipment (PPE) has been limited, increasing their exposure 
risk and causing a significant amount of stress and anxiety for front-line healthcare providers across the 
country.  
 
Back to the Singapore experience, they have used immunoassays that can provide historic information 
about viral exposure, as well as diagnostic evidence. They exploited antibody–antigen recognition, either 
by using monoclonal antibodies (mAbs) to detect viral antigens in clinical samples or by using cloned viral 
antigens to detect patient antibodies directed against the virus. The lateral flow assay format — 
essentially a dipstick encased in a cassette — contains the capture reagents (either an mAb directed at a 
viral antigen or a viral antigen that is recognized by patients’ antibodies) immobilized at defined locations 
on a nitrocellulose membrane, as well as labelled detector mAbs that recognize the same target. A positive 
result, which is triggered by binding between the analyte and capture mAb and binding by the detector 
mAb, is visible as a colored line. Two drops of blood from a pinprick is enough to detect a virus. They’re 
essentially the same as home pregnancy kits. Several of these assays are available in Asia, and most 
European Countries have been using them too. In US, RayBiotech has developed such a similar test using 
knowledge from the Asian tests (https://www.raybiotech.com/covid-19-igm-igg-rapid-test-kit/).  This 
product is CE marked and certified for diagnostic use in the EU. The application for FDA Emergency Use 
Authorizations of tests was submitted on March 16th, 2020. At the moment, the FDA has only approved 
PCR testing. No lateral flow tests have been approved as of March 23rd, 2020. However, this lateral flow 
test can be used legally in the US, for in vitro diagnostic use, as a POC test when administered by a licensed 
medical practitioner. These kits were developed in-house by Ray Biotech and validated using samples 
taken in hospital from patients showing clinical symptoms in Guangzhou China (all confirmed via PCR). 
Current stocks of 10,000 kits are being replenished daily at RayBiotech, with efforts to increase production 
ten-fold 
within 
the 
next 
week. 
The 
CE 
certificate 
can 
be 
found 
here: 
https://www.raybiotech.com/files/images/CG-COV_CE-Certificates.jpg.  
 
Based on the Singapore, Taiwan, Hong Kong positive experience, and to curb the fast spread of the virus 
in the US, we propose to use the POC SARS-CoV-2 IgG Antibody in high risk healthcare workers with or 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
4 
without symptoms, previously quarantine or not. Indeed, we hypothesize that the incidence of 
seroconversion among ER and ICU healthcare workers is high and higher than current models predict and 
that several cases are asymptomatic or with mild symptoms.  
There are two additional benefits of testing seroconversion. 
 
1) Although there are no official reports, we clearly hear and see selfies of anxiety, stress and exhaustion 
from our colleagues at the front line. Thus for the healthcare workers knowing that they have 
seroconverted, will help them be more confident that they are now protected and can work in safer 
conditions as it has recently been shown that reinfection could not occur in SARS-CoV-2 infected rhesus 
macaques  https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.  
 
2) The healthcare workers represent an ideal pool of donors for convalescent plasma due to their 
commitment and the fact that they have usually been tested to give blood or are currently blood donors. 
The FDA just approved a master protocol for collection and administration of convalescent plasma: 
https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-
process-cber/investigational-covid-19-convalescent-plasma-emergency-inds 
 
In sum, “you cannot fight a fire blindfolded, and we cannot stop this pandemic if we don’t know who is 
infected.” (World Health Organization Director-General, 16 March 2020).  
 
If successful and validated, we will hope to rapidly scale it up to propose the rapid SARS-CoV-2 IgG 
Antibody testing to the general population as has been done in countries that have had almost no death 
due to COVID-19.    
 
 OBJECTIVES 
 
 
Primary Objective 
1. To validate the use of a rapid, at home, point-of-care (POC) SARS-CoV-2 IgG antibody test in high 
risk healthcare workers   
 
 
Secondary Objectives  
1. To evaluate the incidence of seroconversion in this high-risk population 
2.    To identify possible candidates for convalescent plasma donation for therapy/prophylaxis 
(https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-
ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds)   
 
 STUDY DESIGN 
This is a non-interventional study to validate the use of a rapid, at home, point-of-care (POC) SARS-CoV-
2 IgG antibody test in high risk healthcare workers. 
 
 ELIGIBILITY CRITERIA  
 
 
Inclusion Criteria: 
1. High risk healthcare workers, prioritizing those who are exposed to aerosol generating 
procedures (physicians and respiratory therapist) working in the emergency room or intensive care 
units at Indiana University Health or IU school of Medicine affiliated facilities.  A second tier of 
prioritization, to be approached if testing capacity remains after the initial testing phase, will be 
nurses working these same areas 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
5 
 
2. Health care workers who are currently out sick or quarantined due to possible/known exposure 
to COVID-19 and whose physician confirms that a negative test would allow their return to work 
are also eligible for testing (Subjects in this group may begin study procedures and be registered 
once they reach the end of their quarantine period) 
 
 
Exclusion Criteria: 
1. Previously tested for COVID-19 
 
 SUBJECT REGISTRATION 
 
All subjects will be registered in OnCore.  Regulatory files will be maintained by the department of 
Pediatrics Intensive Care Unit. Applicable regulatory documents must be completed and on file prior to 
registration of any subjects.  
 
 STUDY PROCEDURES 
          
 
Recruitment and Enrolment  
A recruitment email will be sent out to healthcare workers working at Indiana University and/or 
Indiana University Health (Appendix I) Healthcare workers will be asked to attend walk in hours at 
either Methodist or Riley Hospital in Indianapolis, IN. They will then undergo the informed consent 
process and be registered to study and assigned a unique subject ID.  
 
Subjects will be given a link to complete a short data collection form in REDCAP and will be given the 
SARS-CoV-2 IgG Antibody at home test kit.  
 
 
SARS-CoV-2 IgG Antibody Testing  
The SARS-CoV-2 IgG antibody test will be performed at home by healthcare workers enrolled to 
study.  
 
Figure 1 provides an overview of the testing procedures with detailed instructions provided in the kit 
(Appendix II). Once results are obtained, subjects will send the results to the research team by 
uploading a picture into REDCap or by directly emailing the research team.  
 
 
 
 
 
 
 
 
 
 
 
 
 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
6 
 
Figure 1: SARS-CoV-2 IgG Antibody Testing Workflow 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative IgG Antibody Test Result 
If the test result is negative, there will be no further study procedures and subjects will be advised 
to continue prevention as usual. Subjects may pick up additional tests and re-test with the finger 
prick test in 21 days for a maximum of 3 times.  
 
 
Positive IgG Antibody Test Results 
If the test result is positive, subjects will be instructed to have a blood draw for serological testing 
of IgG to validate the SARS-CoV-2 IgG antibody test. A nasal swab will be performed to confirm 
the absence or presence of virus by PCR. The blood draw and nasal swab will be conducted at an 
IU Health testing site and will be analyzed at the centralized IU Health virology lab.  
 
6.2.2.1 
PCR Positive Results 
If testing is positive and shown to be active for infection by PCR, subjects will be directed 
quarantine per IUH policy. Prevention as usual should continue at work, including the use of 
appropriate personal protective equipment.   
 
6.2.2.2 
PCR Negative Results 
If testing is negative for active infection by PCR and the blood test confirms the results of the 
seroconversion, subjects will be instructed that they may be a candidate for convalescent 
plasma donation via a clinical trial and will be referred to a blood center. This is optional and 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
7 
not mandatory.  Prevention as usual should continue at work, including the use of appropriate 
personal protective equipment.   
 
 COLLECTION OF DATA 
 
Data will be collected from the data collection form completed by subjects and testing results. Data 
captured includes the following: 
• 
Data required for eligibility verification will be collected from subject self-report.  
• 
Demographics (including, age, sex, race/ethnicity, zip code) 
• 
Potential exposure to SARS-CoV-2. 
• 
Clinical symptoms consistent with SARS-CoV-2 
 
 
 DATA FORMS AND SUBMISSION SCHEDULE 
 
Data storage for the study will be performed using a secure, web-based, Research Electronic Data Capture 
(REDCap™). The REDCap® system was developed by Vanderbilt University and is provided by Indiana 
University through their community license. REDCap® is managed by the Indiana University Department 
of Biostatistics and secured by University Information Technology Services (UITS) Advanced IT Core. 
Access to the password-protected database will be limited to the investigators of this study, and any data 
that is distributed will be either de-identified or authorized by written permission from participants. 
 
All source documents are to remain in the subject’s clinic file. All documents will be kept according to 
applicable federal guidelines. Clinical trial data in OnCore® are periodically monitored by the IU Simon 
Cancer Center Data Safety Monitoring Committee.  
 
 
 POTENTIAL RISKS AND PROCEDURES FOR MINIMIZING RISKS 
 
Risks related to blood collection include light headedness, pain, bleeding or infection.  
 
There is also a possible risk of loss of privacy and/or confidentiality. In order to minimize these risks, each 
subject in the database will be assigned a unique study identification (ID) number. Patient-derived 
material will be linked to patient clinical information through this study ID number. All private health 
information (PHI), specimen information, and study data will be entered into the access-controlled, 
password-protected REDCap database. Records and/or data extracted from the database will be identified 
by the subject study ID number only and without any accompanying individually identifiable patient 
information. Thus, the code to the study identification numbers will be accessible only to the PI and 
authorized study personnel. 
 
Emails received from subjects indicating test results will be deleted immediately after receiving or sending 
and after the results are recorded. All messages containing PHI in inbox, sent, or deleted items folder must 
be deleted. Any emails containing PHI may only be sent to an outside environment (non IU, IU Health, or 
Eskenazi accounts) with a valid purpose and will be encrypted.  
 
 
  STATISTICAL CONSIDERATIONS 
 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
8 
The primary objective of this non-interventional study is to validate the use of a rapid, at home, point-of-
care (POC) SARS-CoV-2 IgG antibody test in high risk healthcare workers. Since we do not have a current 
estimate of the seroconversion rate in this high-risk population, we will make a bold estimate that at least 
25% will test seropositive.  We plan to recruit a sample 306 subjects to estimate the seropositive rate with 
95% confident interval of 0.1 width, that if the true rate is 25%, then the sample size is sufficient to obtain 
a 95% CI of [0.2, 0.3]. Assuming the drop-out rate of 10%, then we would need to recruit a total 340 
subjects. The seroconversion rate will be calculated with 95%CI. Additionally, the sensitivity and specificity 
will be calculated with 95%CI. 
 
 
  DATA AND SAFETY MONITORING PLAN  
 
This study will be conducted in accordance with the IU Simon Cancer Center Institutional DSMP for 
Exempt Trials. Investigators will conduct continuous review of data and subject safety.  
 
 DSMC Monitoring & Auditing 
This study will be considered exempt from DSMC review per the IUSCC Institutional DSMP. However, 
the DSMC may elect to require for cause auditing and/or monitoring any time per their discretion. 
 
 Data Management/ Oncore Reporting Requirements 
Despite exemption from DSMC full committee review, this study will comply with the IUSCC Oncore 
Minimum Footprint requirements for study data collection via the OnCore system. 
 
 Study Accrual Oversight 
Accrual data will be entered into the IU Simon Cancer Center OnCore system. The Protocol Progress 
Committee (PPC) reviews study accrual twice per year, while the PPC coordinator reviews accrual 
quarterly. 
 
 Protocol Deviation Reporting 
Protocol deviations will be entered into OnCore within 5 days of discovery. 
 
 
  PATIENT CONSENT AND PEER JUDGMENT 
 
The protocol and informed consent form for this study must be approved in writing by the appropriate 
Institutional Review Board (IRB) prior to any patient being registered on this study.   
 
Changes to the protocol, as well as a change of principal investigator, must also be approved by the Board.  
Records of the Institutional Review Board review and approval of all documents pertaining to this study 
must be kept on file by the investigator (housed in the Clinical Trials Office) and are subject to FDA 
inspection at any time during the study.  Periodic status reports must be submitted to the Institutional 
Review Board at least yearly, as well as notification of completion of the study and a final report within 3 
months of study completion or termination.   
 
 
  CRITERIA FOR REMOVAL FROM STUDY  
The Principal Investigator may withdraw a subject from the study at any time and for any reason. This may 
occur at the discretion of the PI and without the subject’s consent. Examples of why this might occur 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
9 
include: informed consent issues, IRB issues, and discrepancies between samples and associated medical 
information.  
 
 
 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
10 
APPENDIX I: RECRUITMENT EMAIL  
 
We are conducting a research study to determine if high risk healthcare workers have immunity 
to the novel coronavirus, SARS-CoV2.  The purpose of the research is to determine if a certain 
marker in your blood (IgG to SARS-CoV-2) can tell if you have been exposed and now 
recovered from SARS-CoV-2.  About 340 healthcare workers affiliated with Indiana University 
or/and Indiana University Health will take part in this study.   
You are eligible for this study if you work in an area of the hospital that exposes you to aerosol 
generating procedures.  We will first focus on physicians and respiratory therapies working in an 
ICU or ED.   
 
If you have previously been tested for SARS CoV2, you are NOT eligible for this study. 
If you agree to take part in the study, your participation will include 
1. A very short data collection form  
2. A single blood sample taken from a finger prick to be done at home 
a. If you are positive, you will be directed to have a blood draw for serologic testing 
of IgG and validate the rapid test, and a nasal swab at an IU Health testing site to 
confirm by PCR that your infection is not active anymore. 
 
If you are interested in participating in this research study, please attend one of the following 
walk-in hours to be consented and pick up your FREE at home test kit: 
 
XXXXX (to be filled in with the dates and times as we determine them) 
 
Thank you for your consideration, 
Sophie Paczesny and Courtney Rowan, 
 
 
 
 
 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
11 
APPENDIX II: SARS-CoV-2 IgG Antibody Detection Kit Instructions 
 
 
 

PICU-IUSCC-0736 
Protocol Version Date: 03/26/2020 
 
12