Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-28T15:52:33.909Z Has data issue: false hasContentIssue false

Chapter 7 - Development of Assays to Diagnose COVID-19

Published online by Cambridge University Press:  06 January 2024

By
Yukari C. Manabe  and
William Clarke
Edited by
Steven C. Schachter  and
Wade E. Bolton
Steven C. Schachter
Affiliation:
Harvard Medical School
Wade E. Bolton
Affiliation:
VentureWell/Rapid Acceleration of Diagnostics (RADx)
Get access

Summary

This chapter covers the development of diagnostic tests that detect and often amplify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids (molecular tests) or directly detect protein antigens (antigen tests). In the Rapid Acceleration of Diagnostics (RADx®) Tech program, tests that could be performed by following the instructions for use (Clinical Laboratory Improvement Amendments-waived point-of-care tests) or at home (over the counter) became more ubiquitous and represented a paradigm shift in infectious disease diagnostics away from reference laboratory testing by trained laboratorians. Understanding the clinical use case and unmet need is essential to the development of successfully commercialized tests. Important considerations include sample type and collection, the timing of testing (asymptomatic, contact of a known case, or symptomatic), biosafety, the limit of detection and sensitivity, specificity, the turnaround time, form factor and workflow, internal controls, early verification and validation, and supply chain bottlenecks.

Keywords

lateral flow assay (LFA)rapid diagnostic test (RDT)point-of care (POC)over-the-counter (OTC)nucleic acid amplificationturnaround timeClinical Review Committeediagnostic, PCRlimit of detection
Type
Chapter
Information
Accelerating Diagnostics in a Time of Crisis
The Response to COVID-19 and a Roadmap for Future Pandemics
 , pp. 125 - 142
Publisher: Cambridge University Press
Print publication year: 2024

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

FDA, Emergency Use Authorizations for medical devices (June 15, 2023). https://tinyurl.com/msdhfu5a.Google Scholar
Pickering, S., Batra, R., Merrick, B., et al., Comparative performance of SARS-CoV-2 lateral flow antigen tests and association with detection of infectious virus in clinical specimens: a single-centre laboratory evaluation study. Lancet Microbe, 2, 9 (2021), e461–e471.CrossRefGoogle ScholarPubMed
FDA, CLIA waiver by application (May 2, 2022). https://tinyurl.com/yh65vh39.Google Scholar
Code of Federal Regulations, Title 42, Chapter IV, Subchapter G, Part 493 (June 13, 2023). https://tinyurl.com/uhhcaysj.Google Scholar
Ng, O. T., Chow, A. L., Lee, V. J., et al., Accuracy and user-acceptability of HIV self-testing using an oral fluid-based HIV rapid test. PLoS One, 7, 9 (2012): e45168.CrossRefGoogle ScholarPubMed
Weissleder, R., Lee, H., Ko, J., and Pittet, M. J., COVID-19 diagnostics in context. Sci Transl Med, 12, 546 (2020): eabc1931.Google Scholar
Tsang, N. N. Y., So, H. C., Ng, K. Y., et al., Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis. Lancet Infect Dis, 21, 9 (2021), 1233–1245.CrossRefGoogle ScholarPubMed
Savela, E. S., Winnett, A. V., Romano, A. E., et al., Quantitative SARS-CoV-2 viral-load curves in paired saliva samples and nasal swabs inform appropriate respiratory sampling site and analytical test sensitivity required for earliest viral detection. J Clin Microbiol, 60, 2 (2022): e0178521.CrossRefGoogle ScholarPubMed
National Health Service, How to use an NHS COVID-19 rapid lateral flow test (March 21, 2023). https://tinyurl.com/55a7xj6u.Google Scholar
Ke, R., Martinez, P. P., Smith, R. L., et al., Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness. Nat Microbiol, 7, 5 (2022), 640–652.CrossRefGoogle ScholarPubMed
Manabe, Y. C., Reuland, C., Yu, T., et al., Self-collected oral fluid saliva is insensitive compared with nasal-oropharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 in outpatients. Open Forum Infect Dis, 8, 2 (2020): ofaa648.Google Scholar
Wyllie, A. L., Fournier, J., Casanovas-Massana, A., et al., Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2. New Engl J Med, 383 (2020), 1283–1286.Google Scholar
Ranoa, D. R. E., Holland, R. L., Alnaji, F. G., et al., Mitigation of SARS-CoV-2 transmission at a large public university. Nat Commun, 13, 1 (2022), 3207.CrossRefGoogle Scholar
Ke, R., Martinez, P. P., Smith, R. L., et al., Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveals limited infectious virus shedding and restricted tissue distribution. Open Forum Infect Dis, 9, 7 (2022): ofac192.Google Scholar
Gniazdowski, V., Morris, C. P., Wohl, S., et al., Repeated coronavirus disease 2019 molecular testing: correlation of severe acute respiratory syndrome coronavirus 2 culture with molecular assays and cycle thresholds. Clin Infect Dis, 73, 4 (2021), e860–e869.Google Scholar
Liu, R., Yi, S., Zhang, J., et al., Viral load dynamics in sputum and nasopharyngeal swab in patients with COVID-19. J Dent Res, 99, 11 (2020), 1239–1244.Google Scholar
Wölfel, R., Corman, V. M., Guggemos, W., et al., Virological assessment of hospitalized patients with COVID-2019. Nature, 581 (2020), 465–469.Google Scholar
van Kampen, J. J. A., van de Vijver, D., Fraaij, P. L. A., et al., Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat Commun, 12, 1 (2021), 267.Google Scholar
Bullard, J., Dust, K., Funk, D., et al., Predicting infectious severe acute respiratory syndrome coronavirus 2 from diagnostic samples. Clin Infect Dis, 71, 10 (2020), 2663–2666.CrossRefGoogle ScholarPubMed
Killingley, B., Mann, A. J., Kalinova, M., et al., Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults. Nat Med, 28, 5 (2022), 1031–1041.CrossRefGoogle ScholarPubMed
Antar, A. A. R., Yu, T., Pisanic, N., et al., Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in a longitudinally sampled cohort of COVID-19 outpatients. medRxiv (2021), https://doi.org/10.1101/2021.03.02.21252420.CrossRefGoogle Scholar
Arons, M. M., Hatfield, K. M., Reddy, S. C., et al., Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. New Engl J Med, 382, 22 (2020), 2081–2090.CrossRefGoogle Scholar
Furukawa, N. W., Brooks, J. T., and Sobel, J., Evidence supporting transmission of severe acute respiratory syndrome coronavirus 2 while presymptomatic or asymptomatic. Emerg Infect Dis, 26, 7 (2020), e201595.CrossRefGoogle ScholarPubMed
Hoehl, S., Rabenau, H., Berger, A., et al., Evidence of SARS-CoV-2 infection in returning travelers from Wuhan, China. New Engl J Med, 382, 13 (2020), 1278–1280.Google Scholar
Pekosz, A., Parvu, V., Li, M., et al., Antigen-based testing but not real-time polymerase chain reaction correlates with severe acute respiratory syndrome coronavirus 2 viral culture. Clin Infect Dis, 73, 9 (2021), e2861–e2866.CrossRefGoogle Scholar
Siddiqi, H. K. and Mehra, M. R., COVID-19 illness in native and immunosuppressed states: a clinical–therapeutic staging proposal. J Heart Lung Transplant, 39, 5 (2020), 405–407.CrossRefGoogle Scholar
Sethuraman, N., Jeremiah, S. S., and Ryo, A., Interpreting diagnostic tests for SARS-CoV-2. JAMA, 323, 22 (2020), 2249–2251.Google Scholar
Smith, R. L., Gibson, L. L., Martinez, P. P., et al., Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. J Infect Dis, 224, 6 (2021), 976–982.CrossRefGoogle ScholarPubMed
Robinson, M. L., Mirza, A., Gallagher, N., et al., Limitations of molecular and antigen test performance for SARS-CoV-2 in symptomatic and asymptomatic COVID-19 contacts. J Clin Microbiol, 60, 7 (2022), e0018722.Google Scholar
Robinson, M., Gaydos, C., Van der Pol, B., et al., The Clinical Review Committee: impact of the development of in vitro diagnostic tests for SARS-CoV-2 within RADx Tech. IEEE Open J Eng Med Biol, 2 (2021), 138–141.CrossRefGoogle ScholarPubMed
Aspinall, M. G. and Yamashiro, C., Pooling test samples: how and when it works, College of Health Solutions (November 13, 2020). https://tinyurl.com/mr2fvacc.Google Scholar
When to Test, Lab pool testing operational playbook (2022). https://whentotest.org/pooling-playbook.Google Scholar
Berke, E. M., Newman, L. M., Jemsby, S., et al., Pooling in a pod: a Strategy for COVID-19 testing to facilitate a safe return to school. Public Health Rep, 136 (2021), 663–670.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×