Journal article
Comparison of Test-Negative and Syndrome-Negative Controls in SARS-CoV-2 Vaccine Effectiveness Evaluations for Preventing COVID-19 Hospitalizations in the United States
Vaccine, Vol.40(48), pp.6979-6986
10/24/2022
DOI: 10.1016/j.vaccine.2022.10.034
PMCID: PMC9595377
PMID: 36374708
Abstract
•The test-negative design has been widely used for evaluating COVID-19 vaccine effectiveness, yet there is an absence of evidence on comparability with traditional case-control designs.•Despite demographic and clinical differences, the use of test-negative and hospital-based syndrome-negative controls yields similar COVID-19 vaccine effectiveness results.•The test-negative design is a valid approach to estimating vaccine effectiveness against COVID-19 hospitalization.
Test-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.
Adults hospitalized at 21 medical centers in 18 states March 11–August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.
5,811 adults (2,726 cases, 1,696 test-negative controls, and 1,389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64 years, VE was 93% (95% CI: 90-94) using syndrome-negative controls and 91% (95% CI: 88-93) using test-negative controls.
Despite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.
Details
- Title: Subtitle
- Comparison of Test-Negative and Syndrome-Negative Controls in SARS-CoV-2 Vaccine Effectiveness Evaluations for Preventing COVID-19 Hospitalizations in the United States
- Creators
- Caitlin Turbyfill - Centers for Disease Control and PreventionKatherine Adams - Centers for Disease Control and PreventionMark W. Tenforde - Centers for Disease Control and PreventionNancy L. Murray - CDC COVID-19 Emergency Response Team, Atlanta, GeorgiaManjusha Gaglani - Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TexasAdit A. Ginde - Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, ColoradoTresa McNeal - Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TexasShekhar Ghamande - Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TexasDavid J. Douin - Department of Anesthesiology, University of Colorado School of Medicine, Aurora, ColoradoH. Keipp Talbot - Vanderbilt University Medical CenterJonathan D. Casey - Vanderbilt University Medical CenterNicholas M. Mohr - University of IowaAnne Zepeski - University of IowaNathan I. Shapiro - Beth Israel Deaconess Medical CenterKevin W. Gibbs - Department of Medicine, Wake Forest School of Medicine, Winston-Salem, North CarolinaD Clark Files - Department of Medicine, Wake Forest School of Medicine, Winston-Salem, North CarolinaDavid N. Hager - Johns Hopkins University School of MedicineArber Shehu - Johns Hopkins University School of MedicineMatthew E. Prekker - Hennepin County Medical CenterAnne E. Frosch - Hennepin County Medical CenterMatthew C. Exline - The Ohio State UniversityMichelle N. Gong - Albert Einstein College of MedicineAmira Mohamed - Albert Einstein College of MedicineNicholas J. Johnson - University of WashingtonVasisht Srinivasan - University of WashingtonJay S. Steingrub - Baystate Medical CenterIthan D. Peltan - University of UtahSamuel M. Brown - University of UtahEmily T. Martin - University of MichiganAdam S. Lauring - University of MichiganAkram Khan - Department of Medicine, Oregon Health and Sciences University, Portland, OregonLaurence W. Busse - Emory UniversityCaitlin C. ten Lohuis - Emory HealthcareAbhijit Duggal - Cleveland ClinicJennifer G. Wilson - Stanford University School of MedicineAlexandra June Gordon - Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CaliforniaNida Qadir - University of California, Los AngelesSteven Y. Chang - University of California, Los AngelesChristopher Mallow - University of MiamiCarolina Rivas - University of MiamiJennie H. Kwon - Department of Medicine, Washington University, St. Louis, MissouriNatasha Halasa - Vanderbilt University Medical CenterJames D. Chappell - Vanderbilt University Medical CenterCarlos G. Grijalva - Vanderbilt University Medical CenterTodd W. Rice - Vanderbilt University Medical CenterWilliam B. Stubblefield - Vanderbilt University Medical CenterAdrienne Baughman - Vanderbilt University Medical CenterJillian P. Rhoads - Vanderbilt University Medical CenterChristopher J. Lindsell - Vanderbilt University Medical CenterKimberly W. Hart - Vanderbilt University Medical CenterMeredith McMorrow - Centers for Disease Control and PreventionDiya Surie - Centers for Disease Control and PreventionWesley H. Self - Vanderbilt University Medical CenterManish M. Patel - Centers for Disease Control and Prevention
- Resource Type
- Journal article
- Publication Details
- Vaccine, Vol.40(48), pp.6979-6986
- DOI
- 10.1016/j.vaccine.2022.10.034
- PMID
- 36374708
- PMCID
- PMC9595377
- NLM abbreviation
- Vaccine
- ISSN
- 0264-410X
- eISSN
- 1873-2518
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000030, name: Centers for Disease Control and Prevention, award: 75D30121F00002
- Language
- English
- Date published
- 10/24/2022
- Academic Unit
- Epidemiology; Emergency Medicine; Anesthesia; Injury Prevention Research Center
- Record Identifier
- 9984306832802771
Metrics
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