Rapid Expert Consultation on Critical Issues in Diagnostic Testing for the COVID-19 Pandemic (November 9, 2020) (2020) / Chapter Skim
Currently Skimming:
Rapid Expert Consultation on Critical Issues in Diagnostic Testing for the COVID-19 Pandemic (November 9, 2020)
Rapid Expert Consultation on Critical Issues in Diagnostic Testing for the COVID-19 Pandemic (November 9, 2020)
Pages 1-22
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 1... ...
Assistant Secretary for Preparedness and Response 200 Independence Avenue, SW Washington, DC 20201 Dr. Kadlec: Attached please find a rapid expert consultation that was prepared by members and other experts on behalf of the National Academies of Sciences, Engineering, and Medicine's Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats: Jeffrey Duchin, Tara O'Toole, David Walt, Mary Wilson, and me.
|
From page 2... ...
Chair Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats BACKGROUND Goal of This Rapid Expert Consultation The U.S. Food and Drug Administration (FDA)
|
From page 3... ...
Testing Is Part of a Multi-Pronged Mitigation Framework Extensive, strategically deployed SARS-CoV-2 diagnostic testing is an essential aspect of a multi-pronged mitigation plan necessary for the safe resumption of normal social and economic activity now and for some time after a vaccine against SARS-CoV-2 becomes available. In conjunction with physical distancing, masking, and hand washing, adequate availability of prompt and reliable testing is an important public health action needed to contain the spread of the virus through augmenting case and contact management and epidemiological surveillance.
|
From page 4... ...
The scope of this current rapid expert consultation will focus on critical issues in the use of testing to identify current or recent infections in order to control and mitigate viral transmission. The reader is referred to Appendix A for a brief background on antibody tests specific to SARS-CoV-2.
|
From page 5... ...
These include reports from The Rockefeller Foundation and the Duke University Margolis Center for Health Policy that provide tools for policy makers to assess testing approaches and outline legislative and regulatory steps toward a national testing strategy, respectively;4,5 an interactive tool from the Brown University School of Public Health and the Harvard Global Health Institute;6 and a frequently updated list of diagnostic tests that have received EUA.7 Many new diagnostic tests are in various stages of development. The RADx program at NIH, for example, is investing $1.5 billion in better diagnostic tests for COVID-19.
|
From page 6... ...
currently considers a positive antigen test result in asymptomatic patients with low exposure risk as a presumptive case and recommends a confirmatory test by RT-PCR. Like molecular tests, antigen tests are performed on samples obtained from the respiratory tract, for the same reasons explained above.
|
From page 7... ...
Tracing of previous contacts may be needed even if the person who tested RT-PCR positive is not infectious at the time the test result is obtained. But fragments of viral RNA can persist long after viable virus has been cleared.12 When a positive RT-PCR test is obtained 2 weeks or more after an initial infection but not corroborated with the detection of infectious virus in cell culture assays, this may indicate that either the virus level is below the detection limit of culture assays or that the RT-PCR test is detecting remnants of viral RNA rather than intact virus.13 Public health experts have questioned the relevance of RT-PCR tests conducted weeks or months after some individuals have recovered and remained symptom-free, suggesting that a large number of those who "tested positive" may not be contagious.14 In recognition of possibly persistent positive PCR results after an individual is no longer contagious, CDC guidelines no longer recommend that those infected should remain isolated until two sequential, negative RT-PCR results are recorded.
|
From page 8... ...
, the larger the viral load in the sample and the more likely the individual is to be infectious.16 However, Ct values are not routinely reported with clinical results, and the current CDC guidelines recommend against using Ct values to assess infectivity of individuals.17 Preliminary reports have provided good agreement between the correlation of Ct values and positive viral culture,18,19 but there have not yet been enough studies conducted under standard clinical diagnostic conditions that take variability in sampling and testing into account to establish confidence. It is important to note here that RT-PCR assays may be qualitative or quantitative.
|
From page 9... ...
In late July 2020, FDA issued guidance for the performance of "non-laboratory" SARS-CoV-2 diagnostic tests.30 At present, FDA is using RT-PCR as a gold standard of sensitivity and specificity thresholds for comparing diagnostic tests and requiring rapid screening tests, for 22 The United States is currently carrying out an average of 23 million tests monthly from July 2020 to September 2020. Data from https://COVIDtracking.com (accessed September 29, 2020)
|
From page 10... ...
Antigen tests provide fast turnaround times and are inexpensive and relatively easy to manufacture at scale. Such tests may be useful for detecting asymptomatic individuals who may be carrying and able to transmit the virus.
|
From page 11... ...
The results can be displayed on users' smartphones to enable those who test negative to display a "temporary encrypted digital health pass."36 As discussed below, the information value of a testing strategy builds on the performance of an individual test plus the frequency with which tests can be repeated. For example, the cumulative sensitivity of a sequence of regularly repeated tests can be superior to the performance of an intrinsically more sensitive test done only once.37 Verifying the Field Performance of COVID-19 Diagnostic Tests More than 270 different diagnostic tests for COVID-19, of which seven are POC RT-PCR tests that detect nucleic acid and six are POC tests that detect viral antigen, have become commercially available in the United States as of early November 2020.38 On October 7, 2020, FDA announced that it will no longer issue EUA for laboratory-based diagnostic tests and will shift to prioritizing review for POC tests.39 See Appendix B for a list of independently curated databases that track diagnostic tests in various stages of development and approval.
|
From page 12... ...
It has compiled data on diagnostic test performance,44 conducted independent evaluations of molecular tests and immunoassays,45 and maintained a list of diagnostic tests that are commercially available or in development.46 The Center for Systems Biology at Massachusetts General Hospital has also assembled an infographic that provides a brief explanation of different test types, a list of tests that have received EUA, and the reported assay performance data from the manufacturer as well as published field reports.47 Establishing a registry of such data is important for clinical decision making and for selecting the type of tests to use and interpreting the results in screening situations. Role of Government and Public–Private Entities in Expanding POC Testing Government leadership and public–private partnerships are poised to support the large-scale procurement and implementation of rapid, POC tests in the community.
|
From page 13... ...
This is a start toward reaching a national testing capacity, estimated to be at least 30 million each week by November 2020, needed to support a reopening of education, economic, and other social activities through quickly diagnosing infected individuals and their contacts.49 Aggressive screening of asymptomatic individuals as a preventive rather than reactive measure may require up to 14 million tests each day, and frequency as well as strategic test use will differ based on the status of the outbreak control in each situation.50 Additional steps include a bipartisan compact created among 10 states and The Rockefeller Foundation in an effort to induce diagnostic companies to produce sufficient numbers of antigen tests to enable large-scale screening programs that would enable the resumption of social and economic activities while avoiding large-scale outbreaks.51 The members of the compact have pledged to buy POC tests when they become available and to coordinate testing protocols.52 Colleges, universities, and private secondary schools have relied on RT-PCR testing and are also pioneering the use of rapid, POC tests, among other technologies, to detect COVID-19 infections before they trigger outbreaks.53 Additional state testing compacts could catalyze the development of more POC tests; bulk purchasers could help to maintain reasonable pricing of such tests, encourage investment into expanding production capacity to increase overall supply, and avoid the detrimental aspects of states competing against each other while using tests to meet public health needs. It is important to support the expansion of diagnostic testing capacity with actionable public health measures such as contact tracing, wearing face masks, physical distancing, and vigilant hygiene practices and support mechanisms to enhance compliance with isolation and quarantine.
|
From page 14... ...
The target threshold for the sensitivity and specificity of the test may vary for each scenario, as discussed below. Both nucleic acid and antigen POC tests have been reported in developmental studies to have specificity comparable to that for standard RT-PCR tests, although the true specificity in field use may be lower due to factors such as variations in sample collection, operator skill, or off-label use.57 Though they are generally less sensitive than RT-PCR tests, tests that have received EUA so far are designed to diagnose symptomatic individuals, who are likely to have higher viral loads, compensating to some extent for the test's lower sensitivity.
|
From page 15... ...
Augmented Testing Strategies Pooled testing is an approach intended to conserve test resources without sacrificing accuracy where infection prevalence is low. One procedure is called split pool testing and involves "halving" steps.
|
From page 16... ...
COVID-19 Diagnostic Testing Using Next-Generation Sequencing Can Offer a Sensitive and Specific Test with High Throughput NGS offers a highly sensitive and specific test modality with the possibility of providing extremely high throughput rates. Some companies and laboratories have developed COVID-19 testing capacity using NGS that can test up to 10,000 samples at a time with a turnaround time to obtain results in 24–48 hours.
|
From page 17... ...
• There are a number of POC diagnostic tests based on innovative technologies that are in various stages of development and may complement the existing RT-PCR diagnostics system. • Early EUA for laboratory RT-PCR as well as POC tests has been granted based on validation with few, non-standardized, and contrived samples.
|
From page 18... ...
Likewise, CDC currently considers a positive antigen test result in asymptomatic patients with low exposure risk as a presumptive case and recommends a confirmatory test by RT-PCR. Molecular tests provide no other information about a patient's exposure history or their current immune status.
|
From page 19... ...
The simplest tests can be performed with a few drops of blood from a fingerstick. Antibody tests are typically less expensive to manufacture and perform than molecular tests.
|
From page 20... ...
However, investigators in such studies must take care to use tests whose performance has been well characterized to minimize statistical errors in analyzing study data. APPENDIX B Sources for More Information About Tests Additional information on COVID-19 tests and testing can be found in the following sources: • CDC has drafted guidance for the use of COVID-19 tests.74 • The University of Minnesota Center for Infectious Disease Research and Policy provides guidance on testing strategies for using molecular and antibody tests to detect the virus in both symptomatic and asymptomatic people.75 • Carter et al.
|
From page 21... ...
, company, type of specimen, and sensitivity and specificity reported in the EUA records.81 • The Center for Health Security at Johns Hopkins University maintains a COVID-19 testing webpage with a wealth of information, including a list of serology tests.82 • The Joint Research Centre of the European Union has a compilation of COVID-19 test information that have received CE marking.83 APPENDIX C Authors and Reviewers of This Rapid Expert Consultation This rapid expert consultation was prepared by staff of the National Academies of Sciences, Engineering, and Medicine, and members and outside experts on behalf of the National Academies' Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats: Jeffrey S Duchin, University of Washington and Public Health Seattle & King County, Washington; Harvey V
|
From page 22... ...
This activity was supported by a contract between the National Academy of Sciences and the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response (75A50120C00093)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.