@article{b9226cc68ccf4efd89c46a35e54ce21c,
title = "Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts",
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",
author = "Robinson, {Matthew L.} and Agha Mirza and Nicholas Gallagher and Alec Boudreau and Jacinto, {Lydia Garcia} and Tong Yu and Julie Norton and Luo, {Chun Huai} and Abigail Conte and Ruifeng Zhou and Kim Kafka and Justin Hardick and McManus, {David D.} and Gibson, {Laura L.} and Andrew Pekosz and Mostafa, {Heba H.} and Manabe, {Yukari C.}",
note = "Funding Information: This study was funded by the NIH RADx-Tech program under 3U54HL143541-02S2 and U54EB007958-12S1. Funding Information: Editor Yi-Wei Tang, Cepheid Copyright {\textcopyright} 2022 American Society for Microbiology. All Rights Reserved. Address correspondence to Matthew L. Robinson, mrobin85@jhmi.edu. 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, nonfinancial 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. Received 8 February 2022 Returned for modification 27 February 2022 Accepted 17 May 2022 Published 22 June 2022 Funding Information: 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, a research grant from Boehringer Ingelheim, a consulting grant from Avania, nonfinancial research support from Apple Computer, and 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 Bio-Rad, 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. Funding Information: We acknowledge Madison Conte and Elena Konstant for their contributions to the processing and storage of specimens used in this study. 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. This study was funded by the NIH RADx-Tech program under 3U54HL143541-02S2 and U54EB007958-12S1. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Institute of Biomedical Imaging and Bioengineering; the National Heart, Lung, and Blood Institute; the National Institutes of Health, or the U.S. Department of Health and Human Services. Salary support came from the National Institutes of Health U54EB007958-13 (Y.C.M., M.L.R., J.H.), AI272201400007C (A.P., Y.C.M.), UM1AI068613 (Y.C.M.), U54HL143541, R01HL141434, R01HL137784, R01HL155343, R61HL158541, R01HL137734 (D.D.M.). 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, a research grant from Boehringer Ingelheim, a consulting grant from Avania, nonfinancial research support from Apple Computer, and 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. Publisher Copyright: {\textcopyright} 2022 American Society for Microbiology. All Rights Reserved.",
year = "2022",
month = jul,
doi = "10.1128/jcm.00187-22",
language = "English (US)",
volume = "60",
journal = "Journal of Clinical Microbiology",
issn = "0095-1137",
publisher = "American Society for Microbiology",
number = "7",
}