COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave

ABSTRACT Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity...

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Main Authors: Yuan-Po Tu, Christopher Green, Linhui Hao, Alexander L. Greninger, Jennifer F. Morton, Heather A. Sights, Michael Gale, Paul K. Drain
Format: Article
Language:English
Published: American Society for Microbiology 2023-06-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.00064-23
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author Yuan-Po Tu
Christopher Green
Linhui Hao
Alexander L. Greninger
Jennifer F. Morton
Heather A. Sights
Michael Gale
Paul K. Drain
author_facet Yuan-Po Tu
Christopher Green
Linhui Hao
Alexander L. Greninger
Jennifer F. Morton
Heather A. Sights
Michael Gale
Paul K. Drain
author_sort Yuan-Po Tu
collection DOAJ
description ABSTRACT Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ambulatory adults, 626 adult participants were enrolled in a cross-sectional diagnostic study. Each participant had two anterior nasal swabs obtained for rapid antigen and RT-PCR testing and SARS-CoV-2 viral culture. The primary outcomes were the presence and quantification of SARS-CoV-2 growth in VeroE6-ACE2-TMPRSS2 cells in asymptomatic and symptomatic ambulatory adults. In this cross-sectional study of 626 adult outpatients, the sensitivity of a single positive antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with RT-PCR at a cycle threshold CT less than 30 was 66.7% in asymptomatic and 90.7% in symptomatic participants. Among symptomatic participants a with a CT less than 30, a single antigen test had a positive agreement of 90.7% (95% confidence interval [CI], 84.8% to 94.8%). There was 100% negative agreement as all 425 RT-PCR-negative participants had a negative antigen test. A positive antigen test in symptomatic adults with COVID-19 has a strong correlation with replication-competent SARS-CoV-2. Rapid antigen test results may be a suitable proxy for infectiousness. IMPORTANCE Do rapid antigen test results correlate with replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., infectious) virus? In this cross-sectional diagnostic study of 626 adults, the sensitivity of the antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with reverse transcription (RT)-PCR at a CT of less than 30 was 66.7% in asymptomatic participants and 90.7% in symptomatic participants. A positive antigen test may be an appropriate surrogate for identifying replication-competent virus in symptomatic individuals with COVID-19.
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spelling doaj.art-b560b27934a44ec18957335e8984b1262023-06-15T13:18:30ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.00064-23COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta WaveYuan-Po Tu0Christopher Green1Linhui Hao2Alexander L. Greninger3Jennifer F. Morton4Heather A. Sights5Michael Gale6Paul K. Drain7The Everett Clinic – Part of Optum, Everett, Washington, USAAbbott Laboratories, Abbott Park, Illinois, USADepartment of Immunology, Center for Innate Immunity and Immune Disease, Center for Emerging & Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USADepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USADepartment of Global Health and International Clinical Research Center, University of Washington, Seattle, Washington, USAThe Everett Clinic – Part of Optum, Everett, Washington, USADepartment of Immunology, Center for Innate Immunity and Immune Disease, Center for Emerging & Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USADepartment of Global Health and International Clinical Research Center, University of Washington, Seattle, Washington, USAABSTRACT Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ambulatory adults, 626 adult participants were enrolled in a cross-sectional diagnostic study. Each participant had two anterior nasal swabs obtained for rapid antigen and RT-PCR testing and SARS-CoV-2 viral culture. The primary outcomes were the presence and quantification of SARS-CoV-2 growth in VeroE6-ACE2-TMPRSS2 cells in asymptomatic and symptomatic ambulatory adults. In this cross-sectional study of 626 adult outpatients, the sensitivity of a single positive antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with RT-PCR at a cycle threshold CT less than 30 was 66.7% in asymptomatic and 90.7% in symptomatic participants. Among symptomatic participants a with a CT less than 30, a single antigen test had a positive agreement of 90.7% (95% confidence interval [CI], 84.8% to 94.8%). There was 100% negative agreement as all 425 RT-PCR-negative participants had a negative antigen test. A positive antigen test in symptomatic adults with COVID-19 has a strong correlation with replication-competent SARS-CoV-2. Rapid antigen test results may be a suitable proxy for infectiousness. IMPORTANCE Do rapid antigen test results correlate with replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., infectious) virus? In this cross-sectional diagnostic study of 626 adults, the sensitivity of the antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with reverse transcription (RT)-PCR at a CT of less than 30 was 66.7% in asymptomatic participants and 90.7% in symptomatic participants. A positive antigen test may be an appropriate surrogate for identifying replication-competent virus in symptomatic individuals with COVID-19.https://journals.asm.org/doi/10.1128/spectrum.00064-23BinaxNOWCOVID-19COVID-19 antigenreplication-competentSARS-CoV-2SARS-CoV-2 viral cultures
spellingShingle Yuan-Po Tu
Christopher Green
Linhui Hao
Alexander L. Greninger
Jennifer F. Morton
Heather A. Sights
Michael Gale
Paul K. Drain
COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave
Microbiology Spectrum
BinaxNOW
COVID-19
COVID-19 antigen
replication-competent
SARS-CoV-2
SARS-CoV-2 viral cultures
title COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave
title_full COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave
title_fullStr COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave
title_full_unstemmed COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave
title_short COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave
title_sort covid 19 antigen results correlate with the quantity of replication competent sars cov 2 in a cross sectional study of ambulatory adults during the delta wave
topic BinaxNOW
COVID-19
COVID-19 antigen
replication-competent
SARS-CoV-2
SARS-CoV-2 viral cultures
url https://journals.asm.org/doi/10.1128/spectrum.00064-23
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