Seattle Epidemiologic Research and Information Center (ERIC)
CSP #2028 - Study goals and methods
Study goals
The primary goal of this study is to describe the course of SARS-CoV-2 infection and symptomatic COVID-19 disease in Veteran VHA users enrolled into inpatient, outpatient, and Community Living Center (CLC) cohorts and prospectively followed for two years.
Additionally, the study aims to investigate determinants of infection, disease, and the immune response among enrolled Veterans, as well as the effectiveness of treatments and vaccines against SARS-CoV-2/COVID-19. A key contribution of this study is to establish research repositories for clinical and laboratory data, a related research specimen repository, and a participant registry to support future studies of COVID-19 and other health conditions.
Finally, a long-term goal is to provide the lessons learned from this COVID-19 pandemic to better anticipate and manage pandemics in the future for VHA and the general population.
Methods
Study participants
The study consists of three prospectively-followed cohorts: Inpatient, Outpatient, and Community Living Center (CLC). Study operations are coordinated by the CSP Epidemiologic Research and Information Center (ERIC) in Seattle, which oversees enrollment activities across 15 VA medical centers (Baltimore, MD; Boston, MA; Cleveland, OH; Dallas, TX; Denver, CO; Durham, NC; Gainesville, FL; Little Rock, AR; Milwaukee, WI; Palo Alto, CA; Philadelphia, PA; Portland, OR; Salt Lake City, UT; San Antonio, TX; Seattle, WA). Each participating VA medical center serves as a study site and enrolls participants into at least one of the three cohorts. The study’s central laboratory and biorepository are located at the Public Health Reference Laboratory at the VA medical center in Palo Alto, CA. The Seattle ERIC maintains the study’s data repository and participant registry.
Inpatient and Outpatient cohorts: Veterans are invited to participate in the Inpatient and Outpatient cohorts if they have 1) sought care at any of the 15 VA medical centers participating in this study and 2) tested positive for active SARS-CoV-2 infection either at the point of care or during the preceding 21 days. If an eligible Veteran provides consent to participate in this study, the SARS-CoV-2 positive enrollee (alternatively referred to as an exposed enrollee) is invited to complete an enrollment visit (Day 0) and 10 follow-up visits over the subsequent 24 months (Day 3, 7, 14, 21, and 28 and Month 3, 6, 12, 18, and 24). For each exposed enrollee, the study seeks to enroll an unexposed enrollee from among the Veterans who seek care at the same VA medical center, but who have a negative test for active SARS-CoV-2 infection either at the point of care or during the preceding 21-day period. Unexposed enrollees are invited to complete enrollment and subsequent study visits following the same schedule as exposed enrollees.
Enrolled Veterans are assigned to the Inpatient versus the Outpatient cohort based upon whether they are admitted to the hospital at the time of seeking care. The study’s data collection and biospecimen collection schedules are identical for the Inpatient and Outpatient cohorts. At each of the study visits, enrolled Veterans are asked to respond to questionnaires and provide biospecimens. In addition, the study abstracts relevant data from the participant’s electronic health record. In addition to data collected on surveys or from tests run on biospecimens, the study also has the ability to abstract relevant data from the participant’s electronic health record.
CLC cohort: All Veterans living in CLCs located at a subset of the 15 study sites are invited to enroll in the CLC cohort. The members of the CLC cohort are invited to complete an enrollment visit (Day 0) and 8 follow-up visits over the next 24 months (one every 3 months). At each of the study visits, enrolled Veterans are asked to respond to questionnaires and provide biospecimens. In addition, the study abstracts relevant data from the participant’s electronic health record. In addition to data collected on surveys or from tests run on biospecimens, the study also has the ability to abstract relevant data from the participant’s electronic health record.
Study visits
Study Visits are arranged on a schedule with each Visit defined as a range of days after Enrollment (Visit Window). The Visit Window for a particular timepoint spans on either end, to the halfway point between that timepoint and the previous and subsequent timepoints. Each Visit is named for the approximate middle date of the Visit Window. For example, the Month 6 Visit is defined as the range from 136 days after Enrollment (representing the date halfway between Month 3 and Month 6), to 266 days after Enrollment (representing halfway between Month 6 and Month 12).
Questionnaire data
Questionnaires can be administered by study staff either through direct face-to-face interactions or via telephone conversations with enrolled Veterans. Data is entered directly by study staff into the study’s data repository using a customized REDCap electronic data capture system.
MVP COVID-19 Survey: This questionnaire is administered during the enrollment visit. The questionnaire asks participants for information about health, environmental, social, behavioral, and other risk factors for SARS-CoV-2 infection and COVID-19. This questionnaire is adapted slightly from a questionnaire administered to participants of VA’s Million Veterans Program (MVP).
Flu-Related Symptoms Questionnaire: This short questionnaire is administered at each of the study visits. Participants are asked to provide information about influenza-like symptoms experienced in the past 24-hours, using the FLU-PRO® instrument. Several additional questions assess other aspects of the participant’s recent illness and symptoms.
Vaccinations Questionnaire: This short questionnaire is administered at each of the study visits. This questionnaire asks participants to provide information about any dose of SARS-CoV-2 vaccine received, including date of receipt, type/brand of vaccine, and information about the provider who administered the vaccine.
Long-Term Symptoms Questionnaire: This questionnaire is administered at each of the study visits, with the exception of the enrollment visit. The questionnaire involves administering short clinically-validated tools for assessing a participant’s functional status and the occurrence of longer-term COVID-19 symptoms/sequelae based on assessment of health-related quality of life (EQ-5D-5L) and sequelae of SARS-CoV-2 infection, including symptoms of fatigue (PROMIS fatigue 6a), shortness of breath (modified MRC Dyspnea Scale), and cognitive function (PROMIS cognitive function 4a).
Biospecimen collection
The longitudinal collection of biospecimens from participants for the purposes of supporting current and future COVID-19 related studies is a unique contribution of this study to VA research aimed at improving the health of Veterans. To accommodate the observational nature of this study and to reduce the logistical and travel burden to participants associated with the study visit schedule, the study’s protocol allows for both remote and in-person biospecimen collection. Though remote biospecimen collection contributes a lower amount of specimen for research, the participant can perform the collection themselves at a convenient time and place. The devices used for remote specimen collection are designed to preserve the collected specimens during the time that it takes for the enrollee to mail the specimen back to the study’s central laboratory using the pre-paid envelope supplied by the study. Though the vast majority of study visits with members of the CLC cohort involve in-person biospecimen collection, remote specimen collection are permitted from members of this cohort. All of the specimens collected during an in-person visit are shipped on the day of collection to the study’s central laboratory. These shipments are kept at 4-degrees Celsius and scheduled for delivery within 24 hours. All biospecimens sent to the study’s central laboratory are processed immediately upon receipt and preserved in minus-80 degree Celsius research freezers.
Blood samples: At each in-person study visit, participants are asked to provide the following types of venous blood specimens: 23 mL of whole blood in Ethylenediaminetetraacetic acid (EDTA) vacutainer tubes (Purple Top), 10 mL of whole blood in serum separator tubes (SST), 5 mL of whole blood in RNA-stabilizing PAXGene® tubes, and 8.1 mL of blood in citrated plasma tubes. At each remote study visit, participants are asked to provide a microsample of capillary blood (~ 1-5 drops) using a user-friendly collection device manufactured by Tasso®. A subset of the blood specimens collected during an in-person study visit are processed and tested at the VA medical center where the visit occurred, because the particular laboratory tests being conducted must be performed very soon following blood collection.
Respiratory samples: Enrollees of the Inpatient and Outpatient cohorts are asked to provide one of the following types of swabs at each in-person study visit between and including Days 0 and 28: nasal (preferred option), oral, nasopharyngeal, or oropharyngeal swabs. At each study visit, members of the Inpatient and Outpatient cohorts are asked to provide saliva specimens. For in-person study visits, saliva is collected without treatment and shipped directly to the study’s central laboratory. Saliva is collected during a remote study visit using the Spectrum Solutions® SDNA-1000 saliva collection kit, which contains reagents that preserve genetic material at room temperature for an extended period of time.
Stool samples: Stool samples are only collected at in-person study visits with members of the Inpatient and Outpatient cohorts. Stool is collected at the Day 0, 3, 28, and Month 3 study visits using the Zymo Research Corporation’s DNA/RNA Shield® stool collection kit. This kit contains reagents that preserve genetic material in the stool specimen at room temperature for an extended period of time.
Residual clinical specimens: Where available, the study seeks to collect a wide variety of types of residual biospecimens that were collected by VA health care providers to support routine patient care.
