Longitudinal Assessment of Diagnostic Test Performance Over the Course of Acute SARS-CoV-2 Infection
Abstract Background Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages...
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| Published in | The Journal of infectious diseases Vol. 224; no. 6; pp. 976 - 982 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
US
Oxford University Press
30.06.2021
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Abstract
Background
Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented.
Methods
In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture.
Results
Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests.
Conclusions
RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.
Adults newly infected with SARS-CoV-2 were sampled daily for saliva and nasal swab RT-qPCR, Quidel SARS Sofia antigen FIA, and viral culture. We compare test sensitivities at different stages of acute infection and as a function of testing frequency. |
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| AbstractList | Background Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. Methods In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. Results Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. Conclusions RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive. Abstract Background Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. Methods In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. Results Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. Conclusions RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive. Adults newly infected with SARS-CoV-2 were sampled daily for saliva and nasal swab RT-qPCR, Quidel SARS Sofia antigen FIA, and viral culture. We compare test sensitivities at different stages of acute infection and as a function of testing frequency. Adults newly infected with SARS-CoV-2 were sampled daily for saliva and nasal swab RT-qPCR, Quidel SARS Sofia antigen FIA, and viral culture. We compare test sensitivities at different stages of acute infection and as a function of testing frequency. Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented.BACKGROUNDSerial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented.In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture.METHODSIn a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture.Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests.RESULTSBoth RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests.RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.CONCLUSIONSRT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive. |
| Author | Wang, Leyi Baughman, Melinda E Young, Todd Broach, John Conte, Abigail Manabe, Yukari C Pekosz, Andrew Scardina, Kevin R Henness, Darcy Bradley, Shannon Martinez, Pamela P Edmonson, Darci C Heetderks, William J Gloss, Stacy L McManus, David D Robinson, Matthew L Gibson, Laura L Barton, Bruce Lazar, Peter Choi, Hannah Dunnett, Alastair Mostafa, Heba H Chiu, Karen K Owens, Alyssa N Jensen, Tor W Ke, Ruian Gallagher, Nicholas Reinhart, Crystal Smith, Rebecca L Mirza, Agha Brooke, Christopher B Fredrickson, Richard Conte, Madison Yedetore, Jagadeesh |
| AuthorAffiliation | 4 Division of Infectious Diseases and Immunology, Departments of Medicine and Pediatrics, University of Massachusetts Medical School , Worcester, Massachusetts , USA 19 National Institute for Biomedical Imaging and Bioengineering , Bethesda, Maryland , USA 6 Department of Statistics, University of Illinois at Urbana-Champaign , Urbana, Illinois , USA 10 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland , USA 11 Veterinary Diagnostic Laboratory, University of Illinois at Urbana-Champaign , Urbana, Illinois , USA 2 Department of Pathobiology, University of Illinois at Urbana-Champaign , Urbana, Illinois , USA 5 Department of Microbiology, University of Illinois at Urbana-Champaign , Urbana, Illinois , USA 1 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois , USA 15 Department of Emergency Medicine, University of Massachusetts Medical School , Worces |
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| Copyright | The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. |
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| References | Paltiel (2021091718345394400_CIT0012) 2020; 3 Kissler (2021091718345394400_CIT0010) 6 Byrne (2021091718345394400_CIT0011) 2020; 10 Matsuyama (2021091718345394400_CIT0007) 2020; 117 Waggoner (2021091718345394400_CIT0009) 2020; 26 Larremore (2021091718345394400_CIT0013) 2021; 7 Jääskeläinen (2021091718345394400_CIT0003) 4 Moreno (2021091718345394400_CIT0004) Krüger (2021091718345394400_CIT0001) 4 Kucirka (2021091718345394400_CIT0014) 2020; 173 Pray (2021091718345394400_CIT0005) 2021; 69 Ranoa (2021091718345394400_CIT0006) 18 Pekosz (2021091718345394400_CIT0008) Pavelka (2021091718345394400_CIT0002) 2021; 372 |
| References_xml | – ident: 2021091718345394400_CIT0004 article-title: SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing. Clin Infect Dis publication-title: 2021: ciab343 – year: 18 ident: 2021091718345394400_CIT0006 article-title: Saliva-based molecular testing for SARS-CoV-2 that bypasses RNA extraction publication-title: bioRxiv – volume: 69 start-page: 1642 year: 2021 ident: 2021091718345394400_CIT0005 article-title: Performance of an antigen-based test for asymptomatic and symptomatic SARS-CoV-2 testing at two university campuses—Wisconsin, September–October 2020 publication-title: MMWR Morb Mortal Wkly Rep doi: 10.15585/mmwr.mm695152a3 – volume: 7 start-page: eabd5393 year: 2021 ident: 2021091718345394400_CIT0013 article-title: Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening publication-title: Sci Adv doi: 10.1126/sciadv.abd5393 – volume: 173 start-page: 262 year: 2020 ident: 2021091718345394400_CIT0014 article-title: Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure publication-title: Ann Intern Med doi: 10.7326/M20-1495 – year: 4 ident: 2021091718345394400_CIT0001 article-title: Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2 publication-title: medRxiv – volume: 3 start-page: e2016818 year: 2020 ident: 2021091718345394400_CIT0012 article-title: Assessment of SARS-CoV-2 screening strategies to permit the safe reopening of college campuses in the United States publication-title: JAMA Netw Open doi: 10.1001/jamanetworkopen.2020.16818 – volume: 117 start-page: 7001 year: 2020 ident: 2021091718345394400_CIT0007 article-title: Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.2002589117 – ident: 2021091718345394400_CIT0008 article-title: Antigen-based testing but not real-time polymerase chain reaction correlates with severe acute respiratory syndrome coronavirus 2 viral culture publication-title: Clin Infect Dis – year: 4 ident: 2021091718345394400_CIT0003 article-title: Evaluation of three rapid lateral flow antigen detection tests for the diagnosis of SARS-CoV-2 infection publication-title: medRxiv – volume: 372 start-page: 635 year: 2021 ident: 2021091718345394400_CIT0002 article-title: The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia publication-title: Science doi: 10.1126/science.abf9648 – volume: 26 start-page: 1633 year: 2020 ident: 2021091718345394400_CIT0009 article-title: Triplex real-time RT-PCR for severe acute respiratory syndrome coronavirus 2 publication-title: Emerg Infect Dis doi: 10.3201/eid2607.201285 – volume: 10 start-page: e039856 year: 2020 ident: 2021091718345394400_CIT0011 article-title: Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases publication-title: BMJ Open doi: 10.1136/bmjopen-2020-039856 – year: 6 ident: 2021091718345394400_CIT0010 article-title: Viral dynamics of acute SARS-CoV-2 infection publication-title: medRxiv |
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Background
Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely... Background Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely... Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of... Adults newly infected with SARS-CoV-2 were sampled daily for saliva and nasal swab RT-qPCR, Quidel SARS Sofia antigen FIA, and viral culture. We compare test... |
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| SubjectTerms | Antigens Coronaviruses Diagnostic tests Major and Brief Reports Medical diagnosis Polymerase chain reaction Reverse transcription Saliva Severe acute respiratory syndrome coronavirus 2 |
| Title | Longitudinal Assessment of Diagnostic Test Performance Over the Course of Acute SARS-CoV-2 Infection |
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