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. 2022 Jul 20;60(7):e0018722.
doi: 10.1128/jcm.00187-22. Epub 2022 Jun 22.

Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts

Matthew L Robinson  1 , Agha Mirza  1 , Nicholas Gallagher  2 , Alec Boudreau  1 , Lydia Garcia Jacinto  1 , Tong Yu  1 , Julie Norton  2 , Chun Huai Luo  2 , Abigail Conte  3 , Ruifeng Zhou  3 , Kim Kafka  4 , Justin Hardick  1 , David D McManus  5 , Laura L Gibson  5   6 , Andrew Pekosz  3 , Heba H Mostafa  2 , Yukari C Manabe  1
Affiliations

Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts

Matthew L Robinson et al. J Clin Microbiol. .

Abstract

COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases. Close contacts of SARS-CoV-2-positive individuals were enrolled after informed consent. Clinician-collected nasopharyngeal (NP) swabs in viral transport media (VTM) were tested with a routine clinical reference nucleic acid test (NAT) and PerkinElmer real-time reverse transcription-PCR (RT-PCR) assay; positive samples were tested for infectivity using a VeroE6TMPRSS2 cell culture model. Self-collected passive drool was also tested using the PerkinElmer RT-PCR assay. For the first 4 months of study, midturbinate swabs were tested using the BD Veritor rapid antigen test. Between 17 November 2020 and 1 October 2021, 235 close contacts of SARS-CoV-2 cases were recruited, including 95 with symptoms (82% symptomatic for ≤5 days) and 140 asymptomatic individuals. Reference NATs were positive for 53 (22.6%) participants; 24/50 (48%) were culture positive. PerkinElmer testing of NP and saliva samples identified an additional 28 (11.9%) SARS-CoV-2 cases who tested negative by reference NAT. Antigen tests performed for 99 close contacts showed 83% positive percent agreement (PPA) with reference NAT among early symptomatic persons, but 18% PPA in others; antigen tests in 8 of 11 (72.7%) culture-positive participants were positive. Contacts of SARS-CoV-2 cases may be falsely negative early after contact, but more sensitive platforms may identify these cases. Repeat or serial SARS-CoV-2 testing with both antigen and molecular assays may be warranted for individuals with high pretest probability for infection.

Keywords: COVID-19; SARS-CoV-2; rapid diagnostics; test performance.

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Conflict of interest statement

The authors declare a conflict of interest. Becton Dickenson provided Veritor test kits for use in this study but did not contribute to the writing of this manuscript nor critically review its content. D.D.M. reports consulting and research grants from Bristol-Myers Squibb and Pfizer, consulting and research support from Fitbit, consulting and research support from Flexcon, research grant from Boehringer Ingelheim, consulting from Avania, non-financial research support from Apple Computer, consulting/other support from Heart Rhythm Society. L.G.J. is on a scientific advisory board for Moderna on projects unrelated to SARS-CoV-2. H.H.M. reports receipt of research contracts from BioRad, DiaSorin, and Hologic. Y.C.M. has received tests from Quanterix, Becton-Dickinson, Ceres, and Hologic for research-related purposes, consults for Abbott on subjects unrelated to SARS-CoV-2, and receives funding support to Johns Hopkins University from miDiagnostics.

The authors declare a conflict of interest. Becton Dickenson provided Veritor test kits for use in this study but did not contribute to the writing of this manuscript nor critically review its content. DDM reports consulting and research grants from Bristol-Myers Squibb and Pfizer, consulting and research support from Fitbit, consulting and research support from Flexcon, research grant from Boehringer Ingelheim, consulting from Avania, non-financial research support from Apple Computer, consulting/other support from Heart Rhythm Society. LG is on a scientific advisory board for Moderna on projects unrelated to SARS-CoV-2. HHM reports receipt of research contracts from BioRad, DiaSorin, and Hologic. YCM has received tests from Quanterix, Becton-Dickinson, Ceres, and Hologic for research-related purposes, consults for Abbott on subjects unrelated to SARS-CoV-2, and receives funding support to Johns Hopkins University from miDiagnostics.

Figures

FIG 1
FIG 1
Participants enrolled and molecular test results.
FIG 2
FIG 2
Antigen test positivity of contacts. (A) Cycle threshold (CT) values stratified by asymptomatic, symptom onset of ≤5 days, and symptom onset of >5 days for the RT-PCR-positive reference assays, for which there were antigen lateral flow results (n = 99). (B) Culture, antigen result, and CT of reference assay for all RT-PCR-positive NP samples arrayed by early symptomatic (blue shaded), symptomatic (white), and asymptomatic (gray).
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