This section below is a summary of scientific evidence and jurisdictional experiences regarding the sensitivity, specificity and use of rapid antigen diagnostic tests (RADTs) for SARS-CoV-2 as compared with reverse transcription-polymerase chain reaction (RT-PCR) and in relation to the Delta variant for symptomatic and asymptomatic populations including children.

Limitations

One study provided information about the sensitivity of RADTs in detecting the Delta variant. Furthermore, the methodological quality of most of the sources identified are unclear as the Research, Analysis, and Evaluation Branch does not have the expertise to make such assessments; methodological assessments published by other research groups are reported where available (e.g., AMSTAR).

Scientific Evidence

The information in this section consists primarily of findings from four systematic reviews, and five reviews on the sensitivity and specificity of rapid antigen diagnostic tests (RADTs) for both symptomatic and asymptomatic populations. Additional information was drawn from single studies that evaluated specific tests including three single studies that assessed the suitability of RADTs for children.

• Many antigen and molecular rapid tests show high positive predictive values (PPV) and negative predictive values (NPV), reflecting higher likelihoods that a positive test is a true positive and a negative test is a true negative, but these values are affected by the prevalence of the virus where the tests are conducted. For example, PPVs suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Given the variable sensitivity of antigen tests, people who test negative may still be infected.
  • Comparison of RADT and RT-PCR Sensitivity: Typically, the sensitivity of antigen tests is 30% to 40% lower than for RT-PCR tests, depending on whether tested subjects were symptomatic or asymptomatic. The lower sensitive of RADTs is affected by several factors, such as specimen type, the timing of sampling, assay type, and viral load. Overall, clinical sensitivity varies between 28.9% and 98.3%, depending on assay, population characteristics, viral load, and symptom status. Sensitivity in high-viral-load samples (cycle threshold ≤25) showed a considerable heterogeneity among the assays ranging from 66.7% to 100%. Elsewhere, sensitivity from individual studies ranged from 37.7% to 99.2%.
    • Recommendation: The efficacy of any alternative testing strategies to complement nucleic acid-based assays must be carefully evaluated by independent laboratories prior to widespread implementation.
    • Delta Variant: A study of the RADT BinaxNOW found it detected the highly infectious variants including the Delta variant, but test sensitivity decreased with decreasing viral loads. According to the identified literature, sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups.
    • Best Type of RADT: The best RADT sensitivity was found with anterior nasal sampling (75.5% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6% to 74.9%).
  • Specificity of RADTs: Specificity from individual studies ranged from 92.4% to 100.0% but these tests have shown a great range of sensitivities (38.32 – 99.19%).
  • Symptomatic Testing: RADTs vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria can be considered as a replacement for RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. Reliable PPV require testing of symptomatic patients or asymptomatic individuals only in case of a high pre-test probability.
  • Asymptomatic Testing: A systematic review (March 2021) found that evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of RADTs to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A study suggests that, compared with RT-PCRs, RADTs are less effective in asymptomatic populations.
    • Low-Prevalence Testing: If RADTs are used to screen asymptomatic cases in low-prevalence scenarios, a lower positive predictive value of the result must be considered. It is estimated that the likelihood of testing positive in asymptomatic individuals in schools, workplaces, mass gatherings, and travellers would be low (possibly 1 – 2·5%), unless they are in a COVID-19 outbreak area. A RADT with 80% sensitivity and 97% will result in NPVs of 99 – 100% which means that most people testing negative are likely to be true negatives.
  • Testing in Specific Populations: Information was identified about the use of RADTs for children, and for long-term care (LTC) residents.
    • Children: Three single studies reported on the sensitivity of RADTs for children finding that RADTs performed poorly in asymptomatically infected children. One study found an overall suboptimal 66% sensitivity of an assay, ranging between 43% and 73% in asymptomatic and symptomatic children. However, among symptomatic children with high viral load (VL), the assay’s sensitivity was reported to be only marginally lower than symptomatic adults with high VL. It is suggested that RADTs can successfully identify most COVID-19 infections in children with viral load levels likely to be infectious, especially in the first days of the illness. Serial rapid testing may help compensate for limited sensitivity in early infection.
    • LTC Residents: With the high rates of protection of vaccines against symptomatic and asymptomatic SARS-CoV-2 infection, the potential harms and costs of screen testing with RADTs among vaccinated LTC home staff likely outweigh the benefits.
  • Future Research: A Canadian Institutes of Health Research (CIHR) grant application has been submitted by the Ontario SPOR Evidence Alliance to conduct a living systematic review and diagnostic test accuracy network meta-analysis to determine the most sensitive and/or most specific rapid test for COVID-19. It will include both antigen and molecular tests performed in any adult (symptomatic/ asymptomatic/exposed/unexposed/vaccinated/ unvaccinated) and in any setting for COVID-19.

International

Symptomatic Populations

• Australia: Trained health professionals or laboratory scientists use RADTs to test symptomatic patients. RADTs are not intended for home testing, but may be in the future. The Therapeutic Goods Administration (TGA) is undertaking a post-market review of all point-of-care and laboratory tests that identify individuals with COVID-19 to verify whether they can accurately detect emerging variants of concern (VoC). As of August 31, 2021, there are 14 RADT test kits manufactured by different countries that have evidence to support their continued performance with various variants, with 13 of the 14 performing against the Delta variant. The review is ongoing and will be published here as it becomes available.

Asymptomatic Populations

• United Kingdom: Innova lateral flow devices (Biotime SARS-CoV-2 Lateral Flow Antigen Device) is a free test for asymptomatic individuals that provides a quick result using a device similar to a pregnancy test. Tests are available at test sites, pharmacies, schools, universities, and employer sites, and are available for at-home use. Individuals are encouraged to do a rapid test twice a week (every three to four days). If there is a positive result or the test sample could not be read, individuals should do a PCR test. Test results should be reported online within 24 hours of being tested.
  • Findings from three studies (two published by the UK government and one by Liverpool University) on the real-world use of lateral flow devices have confirmed their effectiveness under a variety of conditions (e.g., against VoC, patients with low/high viral loads, mass testing campaigns, hands of inexperienced users, different types of swabs), demonstrating their reliability and adaptability. Specifically, post-market surveillance shows there is no significant difference in the devices’ ability to detect the Delta and Alpha variants.

Symptomatic and Asymptomatic Populations

• United States: As of September 2021, the COVID-19 Action Plan implements a six-pronged, national strategy to combat COVID-19 VoC, one of which is increasing the amount of testing. The production of rapid tests, including at-home tests, will be accelerated via the Defense Production Act and the CAD $2.4 billion procurement of 280 million tests from multiple manufacturers. These tests will be available to support a range of needs, including long-term care facilities, community testing sites, critical infrastructure, shelters serving individuals experiencing homelessness, prisons and jails, and other vulnerable populations and congregate settings. To improve access to rapid tests for all consumers, top retailers that sell at-home, rapid COVID-19 tests (e.g., Walmart, Amazon) will offer to sell those tests at-cost for the next three months, so Americans will be able to buy these tests for up to 35% less.
  • The Food and Drug Administration currently lists many RADTs for emergency use authorization.
• Italy: On February 15, 2021, the Ministry of Health updated the indications regarding the use of RADTs, given the circulation of new variants of the virus, including Alpha and Gamma. Specifically, the new variants should still be detected by antigen tests; however, the situation will have to be closely monitored for other variants (i.e., from the UK and Brazil) RADTs may be used for: close contacts of a confirmed case without symptoms and without others at risk in their household; people displaying milder symptoms; and people arriving from countries at risk. Rapid tests are also the first choice in community screenings, and for those who voluntarily undergo the test for personal reasons, travel, or work needs.

Canada

• The Government of Canada’s interim guidance on the use of RADTs (as of Feb 23, 2021) highlights that VoC have two significant impacts in the potential for deployment of RADTs:
  • Mutations might arise that have a negative impact on the performance of the tests themselves. At the time of writing this guidance, this particular impact had not been observed but it remains an important consideration. Health Canada provides up-to-date risk assessments regarding the impact of VoC on diagnostic assays and requires certain criteria be met before authorizing an application of a RADT.
  • Users should remember 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 (e.g., recent traveller, positive case of COVID-19 following vaccination) should still have a sample collected for PCR testing.
• According to Health Canada’s guidance on testing for COVID-19 in vaccinated populations (August 2021), self-RADTs are not yet authorized for sale in Canada, but several self-RADTs are under consideration with potential regulatory decisions expected by Fall 2021. Depending on the size of a screening program, they may be the most feasible test to use because financial and human resource costs are reduced. As self-RADTs have lower sensitivity than RADTs, follow-up lab-based PCR tests to screen and sequence variants would be required to confirm in initial tests results.

Ontario

• No information identified.

The COVID-19 Evidence Synthesis Network is comprised of groups specializing in evidence synthesis and knowledge translation. The group has committed to provide their expertise to provide high-quality, relevant, and timely synthesized research evidence about COVID-19 to inform decision makers as the pandemic continues. The following members of the Network provided evidence synthesis products that were used to develop this Evidence Synthesis Briefing Note:

• Rapid Point-of-Care Testing for COVID-19. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); December 2020. (CADTH Horizon Scan).
• Ontario SPOR Evidence Alliance (September 17, 2021). Email communication.
• Ontario Health (September 15, 2021). Email communication.
• McMaster Health Forum (September 15, 2021). Email communication.
• Evidence Synthesis Unit, Research Analysis and Evaluation Branch (RAEB), Ontario Ministry of Health. September 20, 2021.