Screening for SARS-CoV-2 in close contacts of individuals with confirmed infection: performance and operational considerations

Background. Point-of-care and decentralized testing for SARS-CoV-2 is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies. Methods. A prospective diagnostic accuracy study was conducted among close contacts of COVID-19 cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and one molecular method were evaluated for usability and performance against reference RT-PCR on NPS. Results. Fifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during at least one visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta emerged increasingly during implementation. Overall sensitivity of evaluated tests ranged from 33% to 76%. Performance was higher among symptomatic cases and cases with Ct<34 and lower among oligo/asymptomatic cases. Assuming a 24-hour time-to-result for RT-PCR, the cumulative sensitivity of an ANS rapid antigen test was >70% and almost 90% after four days. Conclusions. The near immediate time-to-result for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.

[1]  P. Bogaty Rapid Diagnostic Testing for SARS-CoV-2. , 2022, The New England journal of medicine.

[2]  J. Chiche,et al.  Sensitivity of Rapid Antigen Testing and RT-PCR Performed on Nasopharyngeal Swabs versus Saliva Samples in COVID-19 Hospitalized Patients: Results of a Prospective Comparative Trial (RESTART) , 2021, Microorganisms.

[3]  S. Konno,et al.  Performance of Qualitative and Quantitative Antigen Tests for SARS-CoV-2 Using Saliva , 2021, Infectious disease reports.

[4]  A. Galvani,et al.  Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis , 2021, Proceedings of the National Academy of Sciences.

[5]  L. Hooft,et al.  Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study , 2021, BMJ.

[6]  A. Pandey,et al.  Analytical sensitivity and specificity of four point of care rapid antigen diagnostic tests for SARS-CoV-2 using real-time quantitative PCR, quantitative droplet digital PCR, and a mass spectrometric antigen assay as comparator methods. , 2021, Clinical chemistry.

[7]  T. Fekete In adults and children, a rapid POC antigen test for COVID-19 (LumiraDx) had ≥97% sensitivity and specificity vs. RT-PCR , 2021, Annals of Internal Medicine.

[8]  K. Khunti,et al.  Lessons from countries implementing find, test, trace, isolation and support policies in the rapid response of the COVID-19 pandemic: a systematic review , 2021, BMJ Open.

[9]  B. Clotet,et al.  Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial , 2021, The Lancet Infectious Diseases.

[10]  M. Koopmans,et al.  Clinical evaluation of the SD Biosensor saliva antigen rapid test with symptomatic and asymptomatic, non-hospitalized patients. , 2021, medRxiv.

[11]  A. Barbui,et al.  Evaluation of an antigen-based test for hospital point-of-care diagnosis of SARS-CoV-2 infection , 2021, Journal of Clinical Virology.

[12]  M. A. Pisauro,et al.  Containment of COVID-19: Simulating the impact of different policies and testing capacities for contact tracing, testing, and isolation , 2021, PloS one.

[13]  M. Rodríguez-Pérez,et al.  Comparison Between a Standard and SalivaDirect RNA Extraction Protocol for Molecular Diagnosis of SARS-CoV-2 Using Nasopharyngeal Swab and Saliva Clinical Samples , 2021, Frontiers in Bioengineering and Biotechnology.

[14]  L. Hooft,et al.  Rapid, point‐of‐care antigen tests for diagnosis of SARS‐CoV‐2 infection , 2021, The Cochrane database of systematic reviews.

[15]  D. McManus,et al.  Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection , 2021, medRxiv.

[16]  R. Bartenschlager,et al.  Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™: An antigen-detecting point-of-care device for SARS-CoV-2 , 2021, Infection.

[17]  C. Denkinger,et al.  Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis , 2021, medRxiv.

[18]  Q. Bassat,et al.  Performance characteristics of five antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 asymptomatic infection: a head-to-head benchmark comparison , 2021, Journal of Infection.

[19]  I. Bogoch,et al.  The role of asymptomatic and pre-symptomatic infection in SARS-CoV-2 transmission—a living systematic review , 2021, Clinical Microbiology and Infection.

[20]  E. Albert,et al.  Evaluation of a rapid antigen test (Panbio™ COVID-19 Ag rapid test device) for SARS-CoV-2 detection in asymptomatic close contacts of COVID-19 patients , 2021, Clinical Microbiology and Infection.

[21]  S. Hoehl,et al.  The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro , 2021, Journal of clinical medicine.

[22]  P. Glasziou,et al.  Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis. , 2020, Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada.

[23]  D. Larremore,et al.  Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening , 2020, Science Advances.

[24]  A. van Belkum,et al.  Considerations for diagnostic COVID-19 tests , 2020, Nature Reviews Microbiology.

[25]  M. Bergevin,et al.  Efficient SARS-CoV-2 detection in unextracted oro-nasopharyngeal specimens by rRT-PCR with the Seegene Allplex™ 2019-nCoV assay , 2020, Virology journal.

[26]  Georgia Salanti,et al.  Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis , 2020, medRxiv.

[27]  Elizabeth B White,et al.  SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity , 2020, Med.

[28]  Ganna Rozhnova,et al.  Impact of delays on effectiveness of contact tracing strategies for COVID-19: a modelling study , 2020, The Lancet Public Health.

[29]  D. Raoult,et al.  Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards , 2020, European Journal of Clinical Microbiology & Infectious Diseases.

[30]  C. Carey United States food and drug administration , 2020 .

[31]  P. Harris,et al.  Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support , 2009, J. Biomed. Informatics.

[32]  James T. Miller,et al.  An Empirical Evaluation of the System Usability Scale , 2008, Int. J. Hum. Comput. Interact..