Performance of rapid antigen tests to detect SARS-CoV-2 variant diversity and correlation with viral culture positivity: implication for diagnostic development and future public health strategies
Heather Goux,
Jennetta Green,
Andrew Wilson,
Shanmuga Sozhamannan,
Stephanie A. Richard,
Rhonda Colombo,
David A. Lindholm,
Milissa U. Jones,
Brian K. Agan,
Derek Larson,
David L. Saunders,
Rupal Mody,
Jason Cox,
Robert Deans,
Joseph Walish,
Anthony Fries,
Mark P. Simons,
Simon D. Pollett,
Darci R. Smith
Affiliations
Heather Goux
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, Maryland, USA
Jennetta Green
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, Maryland, USA
Andrew Wilson
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, Maryland, USA
Shanmuga Sozhamannan
Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Lead for CBRND Enabling Biotechnologies, Frederick, Maryland, USA
Stephanie A. Richard
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Rhonda Colombo
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
David A. Lindholm
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Milissa U. Jones
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Brian K. Agan
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Derek Larson
Naval Medical Center, San Diego, California, USA
David L. Saunders
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Rupal Mody
William Beaumont Army Medical Center, El Paso, Texas, USA
Jason Cox
C2Sense, Inc., Watertown, Massachusetts, USA
Robert Deans
C2Sense, Inc., Watertown, Massachusetts, USA
Joseph Walish
C2Sense, Inc., Watertown, Massachusetts, USA
Anthony Fries
US Air Force School of Aerospace Medicine, Dayton, Ohio, USA
Mark P. Simons
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Simon D. Pollett
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Darci R. Smith
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, Maryland, USA
ABSTRACT Antigen-based rapid diagnostic tests (Ag-RDTs) provide timely results, are simple to use, and are less expensive than molecular assays. Recent studies suggest that antigen-based testing aligns with virus culture-based results (a proxy of contagiousness at the peak viral phase of illness); however, the performance of Ag-RDTs for newer SARS-CoV-2 variants is unclear. In this study, we (i) assessed the performance of Ag-RDTs and diagnostic antibodies to detect a range of SARS-CoV-2 variants and (ii) determined whether Ag-RDT results correlated with culture positivity. We noted only minor differences in the limit of detection by variant for all assays, and we demonstrated consistent antibody affinity to the N protein among the different variants. We observed moderate to high sensitivity (46.8%–83.9%) for Ag-RDTs when compared to PCR positivity (100%), and all variants were assessed on each assay. Ag-RDT sensitivity and PCR Ct showed an inverse correlation with the detection of viable virus. Collectively, our results demonstrate that commercially available Ag-RDTs offer variable sensitivity compared to PCR, show similar diagnostic validity across variants, and may predict the risk of transmissibility. These findings may be used to support more tailored SARS-CoV-2 isolation strategies, particularly if other studies clarify the direct association between Ag-RDT positivity and transmission risk. The apparent trade-off between sensitivity in the detection of any PCR-positive infection and concordance with infectious virus positivity may also inform new RDT diagnostic development strategies for SARS-CoV-2 and other epidemic respiratory pathogens.IMPORTANCEDespite the availability of vaccines, COVID-19 continues to be a major health concern, and antigen-based rapid diagnostic tests (Ag-RDTs) are commonly used as point-of-care or at-home diagnostic tests. In this study, we evaluated the performance of two commercially available Ag-RDTs and a research Ag-RDT to detect multiple SARS-CoV-2 variants using upper respiratory tract swab samples from clinical COVID-19 cases. Furthermore, we determined whether Ag-RDT results correlated with culture positivity, a potential proxy of viral transmissibility. Our results have important implications to inform future testing and response strategies during periods of high COVID-19 transmission with new variants.
