COVID-19 Antibody and Reinfection Study
Conditions: COVID-19 Testing
Sponsor: Kaiser Permanente

Title: COVID-19 Antibody and Reinfection Study 
 
NCT number: 1589316-19 
Revised: 8/1/2023 
 
 
 
 
 

STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
Goal: 
The goal of this study is to establish a cohort of Kaiser Permanente Colorado (KPCO) members 
who have and have not had COVID-19 infection for serial antibody testing and PCR testing to: 
1. Quantify antibody titers among participants over 9 months. 
2. Determine the rates of recurrent infection among participants with prior COVID-19. 
3. Examine association between antibody titer levels and risk of recurrent infection. 
 
Description: 
In this study, the Kaiser Permanente Colorado (KPCO) Institute for Health Research (IHR) will 
evaluate SARS-CoV-2 IgG antibody titers over time and correlate antibody titers with risk of 
recurrent infection. The investigators will identify KPCO members who have and have not had 
prior infection, enroll them into a cohort study, conduct serial surveys for new COVID-19 
symptoms, and facilitate serial viral and antibody testing.  
 
All laboratory testing procedures and clinical management of participants will be conducted by 
KPCO operations. The research team will identify participants, obtain consent, administer 
surveys to assess COVID-19 symptoms, and direct patients to the appropriate testing. Health 
outcomes on cohort participants will be tracked with survey data on symptoms, clinical and 
utilization data from the KPCO electronic health record (e.g., hospitalization), and laboratory 
data (e.g., viral test results).  
 
This research-operations partnership strategy will generate data to better understand the 
implications of positive antibody titers to this novel pathogen.   
 
Study Type: Observational 
 
Study Model: Case-control nested in a prospective cohort study 
We will recruit participants into a prospective survey and testing cohort who had suspected or 
confirmed SARS-CoV-2 infection. We will also recruit randomly sampled patients of similar age, 
sex, and race/ethnicity with no evidence of previous SARS-CoV-2 infection.  
 
Time Perspective: Prospective 
 
Target Follow-up: 10 months 
 
Study Population: 
The study population will include individuals who are enrolled in KPCO’s health plan.   
Individuals will be selected who have evidence of prior SARS CoV-2 infection and samples of 
the general KPCO membership of similar demographic characteristics who appear not to have 
had SARS CoV-2 infection. 
 
Inclusion criterion:  
• 
KPCO health plan members,  
• 
18 years and older,  
• 
Have a valid email address or phone number in the electronic health record.  
 
Exclusion criterion: 
• 
Opted out of research 
• 
Participated in the pilot survey 

• 
Need a non-English language interpreter 
 
HIPAA Privacy Rule Authorization and Informed Consent Process: 
This study will ask for a waiver of HIPAA Privacy Rule Authorization to identify KPCO members 
who meet the inclusion and exclusion criteria (see above). It is not feasible to outreach this 
cohort without the waiver as the study will include large numbers.    
 
This study will consent eligible members. Participants will be consenting to serial surveys, 
receipt of messaging about testing, and access to antibody testing. This study will consent 
patients electronically through the REDCap e-consenting process. They will also authorize study 
staff to track COVID-19 tests performed, testing results, risk factors for severe COVID-19 
disease, and health outcomes. Participants’ EHR data 24 months prior to enrollment into the 
study and up to 24 months after completing the study may be included the analyses. 
 
Study Procedures: 
 
After identifying and consenting members, we will administer a REDCap initial survey to inquire 
about current symptoms of COVID-19, prior symptoms of COVID-19, prior testing for COVID-19 
(and results), prior or current quarantine or isolation, interest in getting tested, attitudes about 
testing, self-protective behaviors (e.g., social distancing, mask wearing), demographic 
information, employment category, and contact with patients or the public through their 
employment. We anticipate that the survey will take 10 minutes to complete. Follow-up surveys, 
conducted every 28 days, will inquire about new symptoms, new testing, current attitudes and 
current behaviors. Testing procedures and patient notification of viral and antibody results will be 
conducted by operations as part of routine medical care. Operations has notified us that 
antibody results will be made available on KP.org or the KP app. We will inform participants that 
they can obtain results there. 
 
At the time of the baseline or follow-up surveys, based on the responses to questions about 
prior testing and symptoms on the surveys, individuals will be encouraged to seek viral or 
antibody testing.  
 
Participants will receive a thank you email and a second email with instructions for obtaining 
viral and/or antibody testing, depending on their reported previous test(s) and result(s), and 
symptoms.  
 
Participants will be sent a follow-up REDCap survey every 28 days to track symptoms, testing 
and results, quarantine or isolation, attitudes about testing, and protective behaviors. After 
follow-up survey completion, participants will be provided the same instructions about testing, 
based on their responses, as for the baseline. We will conduct repeat antibody testing on 
individuals who test positive to assess for reductions in titer levels over time, and among 
individuals who have negative antibodies to see if they develop new evidence of infection. We 
will conduct repeat viral testing among individuals who report no symptoms in order to assess 
for new asymptomatic infections. 
 
Upon completion of the study, all participants will be sent an “Exit Survey” and testing 
opportunity. After completing the survey, participants will be asked to complete a final nasal and 
antibody test as part of the study.  
 
Protocol Revisions:  
 

Within this cohort, we opted to conduct a nested case-control analysis to examine the 
association between antibody status and reinfection. A nested case-control analysis was 
selected to account for the complexities of pandemic changes over time and various vaccines 
used during the study period. In addition, antibody status (positive/negative) was used instead 
of titer levels, as titer ranges differed across test types. 
 
Data Analysis: 
We will describe the antibody testing results and rates of reinfection among the study 
participants. We will use a nested case-control study design to examine the association 
between antibody seronegativity and reinfection. Reinfection will be defined as a positive SARS-
CoV-2 RNA test ≥ 90 days after the first positive RNA test. Participants with reinfections will be 
matched to controls without reinfections by age, sex, date of the first positive RNA test, date of 
the last serology test, and serology test type. Using conditional logistic regression, case patients 
will be compared to control patients on the last serologic test result, with adjustment for potential 
demographic and clinical confounders.  
 
Privacy, Confidentiality and Data Security: 
The primary protection against a breach of privacy and confidentiality is in the structure of the 
data itself. The data extracted will include the minimum necessary to conduct the described 
research. Additional procedures will be in place to further protect members from a breach of 
confidentiality: 1) all data in study datasets will be identified only by a study-assigned unique ID 
number and will not include the medical record number of the subject; 2) a crosswalk table 
linking the study ID to a patient medical record number will be separately maintained on 
password-protected computers only accessible to study staff; 3) members of the study team 
have completed mandated training procedures and certifications, including special compliance 
training; new research team members (if any) will complete currently mandated training 
procedures and certifications prior to working on the study; and 4) the study protocol will be 
reviewed, approved, and monitored by the IRB. Furthermore, only aggregate data will be 
released in any public forum or publication.  
 
Risks and Benefits: 
This study includes surveys, information about COVID-19 viral and antibody testing, and 
prompts to get viral or antibody testing, including earlier access to antibody testing being offered 
at KPCO.   
 
Participation in the study may give participants with symptoms messaging to get viral testing, 
which may be beneficial for their health and the health of their close contacts. For participants 
who do not have symptoms, they may learn they have been exposed to COVID-19 through 
antibody testing. The harms and benefits of obtaining this information are currently unknown. 
Participants are free to choose whether to get testing. Testing is not a requirement for 
participation. Testing procedures and medical management will be conducted by KPCO 
operations.  
 
The primary risk of this study is the potential for loss of confidentiality and privacy of a member, 
through a loss or inappropriate disclosure of study data. Providing information about a 
member’s COVID-19 symptoms, testing and attitudes may make them feel uncomfortable. They 
can choose to only answer questions that they are comfortable answering. Additionally, there is 
also a small risk for discrimination among individuals who have a positive viral test, a negative 
or positive antibody test, and/or a change in employment location or duties if they disclose the 
results to their employer. Research staff will not disclose the results of any testing conducted 
among individual participants to their managers. There are some inherent physical risks in 

testing from nasal swabs and blood draws. Finally, the tests KPCO makes available may be 
under Emergency Use Authorization and any results should be interpreted with caution.  
Although we will advise them not to, participants may change their behavior as a result of 
positive antibody test results and could put themselves or others at risk for infection if the test is 
inaccurate. Alternatively, participants may have an increase in anxiety if their test results are 
positive or negative. All of these risks described are considered minimal.  
 
There are no known risks to investigators or staff.  The benefits outweigh the minimal risks to 
participants.  
  
Compensation to Participants: 
No compensation will be provided to participants.