Interim guidance on the use of rapid antigen detection tests for the identification of SARS-CoV-2 infection

On this page

• Overview
• Executive summary
• Current approach to SARS-CoV-2 testing in Canada
• Integrating RADTs
  • Test performance
  • Balancing test variables
  • Proposed use cases
  • Deployment in northern, remote and isolated settings
  • RADTs and variants of concern
  • Specimen collection sites
  • Reporting of results
• Knowledge sharing, best practices and external advice
• Endnotes
• Appendix 1

Overview

This document provides interim guidance on the use of rapid antigen detection tests (RADT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These guidelines were developed in collaboration with provincial and territorial public health authorities and will be updated periodically as the science evolves.

This document is the second update of the original version released in February 2021 (updated in July 2022). The use of RADTs for SARS-CoV-2 testing evolved significantly starting in December 2021 as the Omicron variant became the dominant strain. This prompted both an update to this document, as well the development of a technical bulletin to enable a more nimble process to provide information on rapid testing.^{Footnote 1}

Executive summary

• RADTs can play an important role, along with other diagnostic tools, in the response to SARS-CoV-2. RADTs have been deployed in numerous Canadian jurisdictions and around the world.
• Manufacturers continue to monitor test performance with new variants.
• Although these technologies typically have lower sensitivity than molecular tests, they offer additional flexibility in deployment and can extend testing capacity. RADTs have been demonstrated to have high test specificity and rapid turnaround time.
• During periods of high community viral prevalence, when the positive predictive value (PPV) is higher and traditional laboratory test capacity is overwhelmed, this technology can be broadly used. During periods of low prevalence, the positive predictive value is lower and should be considered when making clinical decision based on a positive test.
• Decisions on when and where to implement RADTs should be based on a risk/benefit analysis for the given setting of use.

Current approach to SARS-CoV-2 testing in Canada

Since the emergence of SARS-CoV-2, testing has been a key pillar of Canada's response to the pandemic. Before December 2021, diagnosis relied almost entirely on nucleic acid based testing, commonly referred to as "molecular testing," performed on a nasopharyngeal sample (NP). In order to enhance SARS-CoV-2 testing capacity during the Omicron variant wave, RADTs were widely deployed while molecular testing was largely reserved for high priority populations. Despite this evolution, molecular testing remains the gold standard for detecting SARS-CoV-2 infection in Canada.

Integrating RADTs

RADTs detect proteins from organisms such as viruses and bacteria. They are quick and easy to perform, and the results can be seen in as little as 15 to 30 minutes.

RADTs function as a lateral flow assay, including both a control and antigen specific test line within the result window. After application of an individual's specimen to the test device, the presence of a control line within the results window confirms the validity of the test result, while the presence of a test line is interpreted as positive for the organism. Some technologies require the use of a portable digital reader, while others use an optical readout and format analogous to a disposable pregnancy test.

RADTs can also be used as self-tests, where individuals collect samples for themselves or their dependants and read their results at home.

Canada's COVID-19 Testing and Screening Expert Advisory Panel released a report in August, 2021 on optimizing self-testing.^{Footnote 2} The Panel offered recommendations in the following areas for the use of self-tests: Communication; Equity and Affordability; Use of Self-Testing; and Implementation.

Test performance

The performance of these RADTs can be impacted by a number of variables, including symptom status, viral load, and the sampling collection method (e.g. NP versus nasal). Correct interpretation of test results is also critical for effective utilization. This issue can be particularly pronounced for those who are new to using the tests, and have limited experience in the range of band intensity.

Specificity of RADTs is typically excellent, while sensitivity tends to be more of a concern. A 2021 Cochrane review found that while specificity for all tests considered was high (~99%), sensitivity was lower.^{Footnote 3} The tests were found to be 73% sensitive in people with symptoms, and 54% sensitive in people without symptoms. Furthermore, sensitivity was 95% among individuals with high viral loads compared to 41% among individuals with lower viral loads. These findings are consistent with internal National Microbiology Laboratory (NML) data demonstrating improved concordance between RADTs and molecular tests in samples with higher viral loads. The data on performance of RADTS on new SARS-CoV-2 Omicron variants suggests lower sensitivity, which can be mitigated through repeated testing or PCR confirmation for patients in high-risk groups. This data comparing the Delta and early Omicron strains can be viewed in Appendix 1.

A visual comparison demonstrating the timelines of antigen and molecular test positivity during acute infection can also be seen in an article by Drain in the January 20, 2022 edition of the New England Journal of Medicine."^{Footnote 4}

Balancing test variables

When considering use of RADTs, a balance between lower overall sensitivity and other beneficial characteristics (e.g., faster turnaround time, lower test cost, options for testing by non-professionals) point to a number of settings where the use of these tests can and should be considered.

The intrinsic performance characteristics of a test are not the only factors determining its utility. The final interpretation of a test must take into account factors such as the prevalence of infection, clinical symptoms, and the intended use of the test result. Therefore, the tolerance for sensitivity and specificity thresholds for a given type of test will vary based on the reason for ordering the test and the expected action that would follow either a positive or a negative test.

Analyses have concluded that for viruses with infection kinetics similar to SARS-CoV-2, the most critical aspects in responding to an outbreak are speed of reporting and the impact of repeated population screening.^{Footnote 5} The emergence of early treatment options for SARS-CoV-2 such as antivirals, which have the greatest effectiveness when administered as early as possible, further support the need for the implementation of rapid test options such as RADTs. To overcome the reduced sensitivity of early infection most jurisdictions recommend that symptomatic individuals repeat the antigen test after 48 hours. While this will improve detection rates as the viral load increases to levels above the RADTs level of detection, there are data to suggest that this varies and can be >48 hours before RADTs can detect infection.

One important variable in understanding test utility is viral prevalence. For example: At 5% prevalence, positive predictive values (PPVs) of 84% to 90% mean that approximately 1 in 8 results will be a false positive. At 0.5% prevalence, applying the same tests would result in PPVs of 11% to 28%, meaning that approximately 8 in 10 positive results will be false positives. In scenarios of higher viral prevalence, positive tests can typically be considered true positives and acted on without further confirmation, while negative tests may warrant a subsequent confirmatory test. The reverse is true when pre-test probability is low: negative tests can be considered true negatives, while positive tests may warrant a confirmatory test.

Another important variable that can influence the implementation of RADTs is the level of public engagement. One study that assessed the human component in testing found that 79% of participants were generally willing to use home tests, while 21% of participants were not.^{Footnote 6} Most study participants planned to use a RADT if either symptomatic (70%), or in contact with a case (63%). Willingness to test increased with the belief that testing and isolation can slow the pandemic and protect others, and related partially to trust in government. Two key motivations identified against testing were not understanding why and/or how to test, and doubts regarding test validity. Willingness to home test was less likely in those believing COVID-19 is not dangerous.

Proposed uses

The WHO has recommended in its October 2021 updated guidance that RADTs meeting minimum performance requirements can be used for primary case detection, contact tracing during outbreak investigations, and to monitor trends of disease incidence in communities.

"In all settings, the first priority of COVID-19 control is to deploy available financial and human resources toward the prompt identification of SARS-CoV-2 in symptomatic individuals and contacts of confirmed or probable cases and enable them to be compliant with countermeasures including isolation. If correctly performed and interpreted, RADTs can play a significant role in this effort and may be more cost effective than NAAT in symptomatic populations."^{Footnote 7}

There are a number of potential uses for RADTs that have been explored to date, serving different goals. It should be emphasized that these expanded uses are meant to supplement the existing testing capacity in Canada and should be implemented with close linkage to local systems and public health.

The WHO guidance recommends three settings likely to have the most impact on early detection of cases for antivirals and care and contact tracing:

• Community testing of individuals with COVID-19 symptoms meeting the case definition of suspected COVID-19.
• Detecting and responding to suspected outbreaks of COVID-19
• Screening individuals who are asymptomatic and at high risk of COVID-19, including health care workers and contacts of cases.

Other settings where the WHO recommends additional research to refine the role of RADTs include travellers, workplaces and schools.

RADTs are also potentially useful when testing individuals who are highly mobile or who may not access health care frequently. For example, rapid results can help with public health management and engagement in the cases of individuals who are transient, have precarious living conditions, or are experiencing homelessness

Some of the advantages of these approaches include:

• Building capacity in communities across the province through engagement, education, and empowerment;
• Increasing awareness of the importance of testing as a public health measure;
• Engaging the community to reinforce the ongoing public health measures to help mitigate transmission
• Destigmatizing and increasing testing for all populations.

In scenarios where critical decisions and actions rest on the identification of SARS-CoV-2 (e.g. ICU patients who would benefit from COVID-specific therapeutics), the recommended test would be the most sensitive test, which remains a laboratory based molecular test.

Deployment in northern, remote, and isolated settings

Northern, remote and isolated (NRI) settings face additional barriers to timely test results due to transportation logistics. This makes RADTs a potentially useful option as an initial test in these communities. However, given the importance of identifying new cases in NRI communities and the recent widespread distribution of on site platforms (e.g. GeneXpert), molecular testing is often recommended for these settings. Nonetheless, there remains ongoing training and quality assurance requirements in smaller health centres for implementing these testing approaches.

RADTs tend to be low complexity tests since they are single use and have a visual indicator. This translates to RADTs being a useful option as an initial test. If positive, presumptive action can quickly be put in place. Since remote settings are particularly vulnerable to outbreaks of COVID-19, given the limited health care resources, there should be additional consideration for confirmatory molecular testing. As remote settings are particularly vulnerable to outbreaks of COVID-19, there should be additional consideration for linkage to an accredited laboratory for confirmatory testing activities and laboratory support.

RADTs and variants of concern

Numerous variants of concern (VoC) have arisen across the globe. VoC can have significant impacts on the potential for deployment of RADTs, in particular if mutations arise that have a negative impact on the performance of the tests themselves. To date, all variants have been detected via commonly used RADTs in Canada.

Another factor related to VoC in the context of RADT use is the fact that sequencing characterization cannot be done from a RADT device. As a result, it is important to ensure that individuals with a positive RADT result that may require further characterization (such as a recent international traveller) also have a sample collected for confirmatory molecular testing and sequencing.

Work is ongoing with manufacturers of approved COVID-19 test devices to assess the impact of novel variants of public health concern. Manufacturers who identify a concern about the performance of their test as a result of a novel variant are expected to report these concerns.

Sampling collection methods

Initially in the COVID-19 pandemic, diagnostics focused on NP sampling. Alternative sampling sites including nose, throat and saliva were examined throughout the pandemic. A Canadian study found that use of combined throat/nares significantly increased detection over either site alone.^{Footnote 8}

It is important for users of RADTs to follow the manufacturer's recommended collection processes. However, this will not always occur, such as in situations where the manufacturer's recommendations do not keep pace with the rapidly evolving science. Nimble processes to incorporate new evidence into regulatory mechanisms and public health recommendations will need to continue into the future.

Reporting of results

The use of RADTs occurs outside of the laboratory environment. Therefore, an additional variable that should be considered is the reporting of positive results into the public health system. The integration of test results into laboratory systems and patient records are important aspects in ensuring appropriate data capture, quality control, and clinical/public health follow-up.

Knowledge sharing, best practices and external advice

There has been a great deal of information generated in the use of RADTs, with a number of approaches supporting different but complementary public health goals. In drafting the present iteration of the recommendations herein, consultation has leveraged the knowledge exchange at the level of the Canadian Public Health Laboratory Network and a number of federal, provincial and territorial committees. These processes will continue as the pandemic response moves forward and will enable further updates to these guidelines as the science evolves and new technologies come to market. It is critical to continue to gather information about deployment strategies and their impact.

Appendix 1

Table 1: Performance of 11 approved COVID-19 rapid tests using 15 patient samples identified as the Delta or Kappa variant

This table shows the performance of 11 approved COVID-19 rapid tests using 15 patient samples identified as the Delta or Kappa variant. The symbol "+" indicates a positive test result, and "-" indicates a negative test result. Tests include: the Cepheid GeneXpert^® Xpert^® Xpress^® SARS-CoV-2/Flu/RSV Assay (GeneXpert), BTNX Rapid Response^® COVID-19 Antigen Rapid Test (Rapid Response), Abbott PanBio™ COVID-19 Ag Rapid Test Device, BD Veritor™ System for Rapid Detection of SARS-CoV-2, Roche SD Biosensor COVID-19 Ag Test (SD Biosensor), Roche SARS-CoV-2 Rapid Antigen Test Nasal (Roche SCV2), Quidel^® QuickVue^® At-Home OTC COVID-19 Test, Artron Laboratories Inc. COVID-19 Antigen Test, Abbott ID Now™ COVID-19 Assay, and Lucira™ CHECK IT COVID-19 test kit.BD Veritor tests were interpreted visually as well as with the provided analyzer. Samples were blinded before testing, and each test was interpreted independently by three experienced laboratory personnel (shown as 1,2,3 below).

Sensitivity of rapid antigen tests for detection of SARS-CoV-2 Omicron variant

Table 2: Performance of 11 approved COVID-19 rapid tests using 20 patient samples identified as the Omicron variant

This table shows the performance of 11 approved COVID-19 rapid tests using 20 patient samples identified as the Omicron variant. The symbol "+" indicates a positive test result, and "-" indicates a negative test result. Tests include: the Cepheid GeneXpert^® Xpert^® Xpress^® SARS-CoV-2/Flu/RSV Assay (GeneXpert), BTNX Rapid Response^® COVID-19 Antigen Rapid Test (Rapid Response), Abbott PanBio™ COVID-19 Ag Rapid Test Device, BD Veritor™ System for Rapid Detection of SARS-CoV-2, Roche SD Biosensor COVID-19 Ag Test (SD Biosensor), Roche SARS-CoV-2 Rapid Antigen Test Nasal (Roche SCV2), Quidel^® QuickVue^® At-Home OTC COVID-19 Test, Artron Laboratories Inc. COVID-19 Antigen Test, Abbott ID Now™ COVID-19 Assay, and Lucira™ CHECK IT COVID-19 test kit. Veritor tests were interpreted visually as well as with the provided analyzer. Samples were blinded before testing, and each test was interpreted independently by three experienced laboratory personnel (shown as 1,2,3 below).

Table 3: Performance of approved COVID-19 RADTs using five patient samples identified as COVID-19 negative

This table shows the performance of approved COVID-19 RADTs using five patient samples identified as COVID-19 negative. The symbol "-" indicates a negative test result. Tests include: the Cepheid GeneXpert^® Xpert^® Xpress^® SARS-CoV-2/Flu/RSV Assay (GeneXpert), BTNX Rapid Response^® COVID-19 Antigen Rapid Test (Rapid Response), Abbott PanBio™ COVID-19 Ag Rapid Test Device, BD Veritor™ System for Rapid Detection of SARS-CoV-2, Roche SD Biosensor COVID-19 Ag Test (SD Biosensor), Roche SARS-CoV-2 Rapid Antigen Test Nasal (Roche SCV2), Quidel^® QuickVue^® At-Home OTC COVID-19 Test, Artron Laboratories Inc. COVID-19 Antigen Test, Abbott ID Now™ COVID-19 Assay, and Lucira™ CHECK IT COVID-19 test kit.BD Veritor tests were interpreted visually as well as with the provided analyzer. Samples were blinded before testing, and each test was interpreted independently by three experienced laboratory personnel (shown as 1,2,3 below).