A study to define unmeasured transmission and estimate potential for protecting nursing home residents through serologic assessments of nursing home staff.
Study Background
SARS-CoV-2
The novel coronavirus, SARS-CoV-2, first emerged in Wuhan, China in early December 2019, and has been described to cause a severe and acute respiratory syndrome, now named COVID-19. By March 11, 2020, the World Health Organization (WHO) declared that the extent of Covid-19 spread had reached pandemic proportions. As of October 8, 2020, the WHO reported 207 countries affected by COVID-19, with 36,002,827 confirmed cases and 1,049,810 confirmed deaths. In the United States, there have been almost 7,419,230 cases with at least 209,450 deaths as of October 8, 2020. Although there are clinical trials underway to investigate therapeutic options, supportive care is currently the mainstay of treatment at this time. SARS-CoV-2, causes a range of clinical disease severity, from mild upper respiratory disease to death. Overall fatality rates have varied based on case definitions and total sample tested and have ranged from 1.4-2% and as high as 30% in Skilled Nursing Facility (SNF) residents.
Skilled Nursing Facilities
For this study, we will focus on SNFs, defined by the Centers for Medicare and Medicaid Services (CMS) as institutions, such as skilled nursing homes or rehabilitation centers, primarily engaged in providing skilled nursing care and related services for residents who require medical or nursing care; or rehabilitation services for the rehabilitation of injured, disabled, or sick persons. The SNF setting has proven to be particularly vulnerable to rapid spread of SARS-CoV-2 among residents and staff because of the congregate living environment, frail population, need for assistance with many activities of daily living, and the potential for virus transmission among asymptomatic individuals. Additionally, older adults infected with SARS-CoV-2 may not present with typical symptoms and residents in the SNF setting may have more difficulty communicating changes in health status because of underlying dementia or other cognitive or functional impairment.
Guidance for Skilled Nursing Facilities
Initial guidance for managing SARS-CoV-2 in the SNF setting focused on limiting visitation, determining staffing protocols, implementing infection control procedures, and promoting resident-centered care in the setting of increased isolation from social networks. However, SNF staff, including healthcare personnel (HCP), may introduce the virus when symptomatic, pre-symptomatic, or asymptomatic. Currently CDC guidelines recommend universal temperature checks with self-reporting of symptoms, as well as universal masking for all SNF staff to prevent such transmission; some facilities augment this with the use of universal face-shields or other efforts such as periodic nasal screens for viral PCR. Currently, CMS requires routine testing for virus among HCP and residents using PCR to detect virus, but does not suggest or mandate any antibody testing.
Antibody Testing
Antibody testing can be done using serology tests that measure antibodies to SARS-CoV-2 (e.g. IgM and IgG) will be essential to better quantify exposure, and to identify particular groups of HCP who may be at higher risk of infection. Current diagnostics, such as real-time polymerase chain reaction (RT-PCR), are effective for quantifying viral material and diagnosing acute infection. Viral load, and thus detection via RT-PCR, has been shown to peak during the first week of symptoms, and then decline. In contrast, antibody serological assays provide information regarding an individual’s exposure and likely immunity to SARS-CoV-2. Several assays are being developed, most of which target the large glycoprotein spike protein (S) of the SARS-CoV-2 virion, which guides binding to host cells by interactions with the human receptor angiotensin converting enzyme 2 (ACE2). The rate of seroconversion and seroprevalence in a population can be determined using these assays.
Rationale
By determining the rate of seroconversion in HCP using serological testing, and leveraging data on metrics of infection in residents from routine testing reports in a sample of SNF facilities, we will be able to estimate how frequently transmission has occurred among these populations. Furthermore, serological assays may permit an understanding of HCPs who are immune, and thus could provide insights into future strategies to mitigate risk to non-immune HCPs or be able to ration personal protective equipment (PPE) more specifically and appropriately.
The pandemic caused by the novel SARS-CoV-2 virus has caused significant morbidity and mortality, particularly among SNF residents and HCPs. This study is crucial to determine the degree of unrecognized infection among SNF HCP in the context of a variety of community incidence levels and resident disease prevalence. An understanding and characterization of the prevalence and incidence of SARS-CoV-2 infection in this important population will better inform health care practices and infection prevention measures in times of pandemic disease.
Study Objectives
Primary:
- Estimate the cumulative infection incidence with SARS-CoV2 among residents and HCP of skilled nursing facilities (SNF) in Georgia.
Secondary:
- Quantify and identify drivers for the discordance between reported SARS-CoV-2 infections by PUI/PCR testing (e.g., since February), and serologic evidence of infection among SNF HCP in sampled SNFs.
- Evaluate the potential for protecting residents through staffing decisions based on serology-status at SNFs using mathematical models.
- Bank specimens for further studies.
Testing Procedure
Study personnel will obtain informed consent from approximately 1,700 participants and collect an initial dried blood spot (DBS) sample for serology testing. The test being used in this study is the EUROIMMUN SARS-COV-2 ELISA (IgG) test. This test has been evaluated and approved for use by the Food and Drug Administration (FDA) which has published the following performance metrics for the EUROIMMUN test being used in this study:
Antibody | Performance Measure | Estimate of Performance | 95% Confidence Interval |
IgG | Sensitivity | 90.0% (27/30) | (74.4%, 96.5%) |
IgG | Specificity | 100% (80/80) | (95.4%, 100%) |
IgG | PPV at prevalence = 5% | 100% | (46.1%, 100%) |
IgG | NPV at prevalence = 5% | 99.5% | (98.6%, 99.8%) |
Test recipients can find out more about the EUROIMMUN SARS-CoV-2 antibody test by exploring the FDA's Recipient Factsheet and healthcare providers can find further information from the FDA's Factsheet for Healthcare Providers. More information on test performance, including the data presented in the table can be found at the FDA's EUA Authorized Serology Test Performance webpage.
Study Timeline
September 2020
Recruitment
At enrollment, HCPs across 14 participating locations will provide informed consent, complete a baseline survey, and submit a dried blood spot (DBS) specimen for serological testing.
January 2021
Follow-Up Serology (4 months)
An optional midpoint serology specimen will be collected based on availability and willingness of study participants and other operational considerations of the study.
February 2021
Follow-Up Survey (6 months)
Follow-up surveys to assess ongoing exposure risk will employ the same mechanism as the baseline survey and occur every month through 6 months to HCP enrolled in the study.
Study Team
Co-Principal investigators Dr. Scott Fridkin, MD and Dr. Benjamin Lopman, PhD lead a multidisciplinary team of scientists, students, and administrators.
Additional Resources
For Study Participants
- Considerations for Interpreting Antigen Test Results in Nursing Homes
- FDA EUROIMMUN Factsheet for Test Recipients