COVID-19 Health Alert # 17:
Bureau of Communicable Diseases, September 24, 2020
- A number of assays for rapid SARS-CoV-2 antigen detection have received emergency use authorization (EUA) from the U.S. Food and Drug Administration. While antigen tests are less expensive and have a shorter turnaround time than most molecular tests (e.g., RT-PCR), they are less accurate and results should be interpreted carefully.
- Rapid SARS-CoV-2 antigen tests perform best when used for diagnosis of COVID-19 in patients with symptoms of acute respiratory infection. Positive tests in symptomatic patients, or when there is a high pre-test probability (e.g., in outbreak settings or among close contacts of exposed cases), should be considered presumptive evidence of infection and do not require confirmatory testing. Because of the risk of false negative results, symptomatic patients who have a negative antigen test result should be re-tested with an alternative method to confirm the result.
- The use of SARS-CoV-2 antigen tests for screening asymptomatic persons was not included in the FDA Emergency Use Authorization. Antigen testing of patients without symptoms is therefore considered “off-label” use and is not recommended for routine screening. FDA has provided guidance, however, that such off-label use may be appropriate in some settings where access to highly sensitive tests is inadequate.
- If used for asymptomatic screening, SARS-CoV-2 antigen tests are expected to result in a high proportion of false positive results. A two-test strategy is therefore required in order to yield reliable results in this setting. All positive antigen results obtained from asymptomatic, non-close contacts should be followed by a different test as soon as possible and within 48 hours. Presumptive negative results do not need confirmation testing in this setting.
- Providers and organizations using SARS-CoV-2 antigen tests should be aware of all reporting requirements for COVID-19. All positive antigen results should be reported to local public health departments. Negative antigen test results are not required to be reported to the state but still need to be reported to HHS.
Rapid SARS-CoV-2 antigen tests have become increasingly available and are now part of the available testing response to the COVID-19 pandemic. Health care providers, health systems, and laboratories should be aware of the characteristics of the available tests, including reduced sensitivity and specificity, which may limit their usefulness in certain circumstances. The CDC has recently updated its website, Interim Guidance for Rapid Antigen Testing for SARS-CoV-2, which provides additional information about the use of antigen tests for diagnostic, screening, and surveillance purposes.
Molecular tests that detect viral RNA, specifically RT-PCR, remain the “gold standard” for clinical diagnostic detection of SARS-CoV-2 because of their high level of accuracy. RT-PCR tests are in widespread use across the state, which has a current estimated daily capacity of over 38,000 tests in Wisconsin’s clinical and commercial laboratories, but they have important limitations including variable turnaround time and potential supply limitations of specimen collection equipment and laboratory reagents.
Antigen tests have drawn interest as an alternative method to complement and expand the existing testing resources, including large procurements by the federal government for use in long-term care and educational settings. Antigen and other point-of case-tests offer several advantages in comparison to standard molecular tests as they are relatively inexpensive, can be used at the point of care, and can provide rapid results in 15 minutes or less.
Characteristics of SARS-CoV-2 Antigen Tests Currently Available
Antigen tests that are currently authorized for use are immunoassays that target the SARS-CoV-2 nucleocapsid proteins. They provide rapid, qualitative results indicating the presence of the virus in a specimen. Antigen test are typically performed on nasopharyngeal or nasal swabs directly from the patient. Samples should not be diluted in viral transport media prior to testing and should be tested as soon as possible from the time of collection. With the exception of the Abbott BinaxNOW™ COVID-19 Ag Card, the available antigen tests involve a separate instrument to read the results. The antigen tests, which have received emergency use authorization by the FDA, are listed in Table 1. All four of these tests can be used outside of laboratory settings in patient care areas that have been granted a Certificate of Waiver under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
Table 1. SARS-CoV-2 antigen tests currently authorized for use in the United States
|Test Name||Instrument Required||Specimen Types||Sensitivity*||Specificity*|
|Quidel Sofia 2 SARS Antigen FIA||Sofia 2 FIA Analyzer||Direct NP or Nasal Swabs (supplied with kit);
Collect within 5 days of symptom onset
|BD Veritor System for Rapid Detection of SARS-CoV-2||BD Veritor Plus Analyzer||Direct Nasal Swabs (supplied with kit);
Collect within 5 days of symptom onset
|LumiraDx SARS-Cov-2 Ag Test||LumiraDX Instrument||Direct Nasal Swab;
Collect within 12 days of symptom onset
|Abbott BinaxNOW COVID-19 Ag Card||None||Direct Nasal swab (supplied with kit);
Collect within 7 days of symptom onset
*Estimates of sensitivity and specificity are derived from data reported to the FDA, based on limited testing in symptomatic people. The performance of these tests may vary when used in diverse “real world” settings, and when used for asymptomatic people.
Considerations for Use of Antigen Tests in Symptomatic and Close Contact Patients
In settings where there is a high pre-test probability of COVID-19 disease, such as a person exhibiting signs and symptoms of acute respiratory infection or a person who has been in close contact with someone known to have COVID-19, antigen tests can provide rapid diagnostic information needed to inform immediate clinical decisions or infection control measures such as isolation and quarantine. When deployed in settings where molecular testing is not readily available, antigen test results can support such decision-making without the need for confirmatory testing of positive results. The reported sensitivity of antigen tests ranges from 84.0%-97.6% compared to RT-PCR, based on initial data submitted to the FDA.
Negative test results may be insufficient to definitively rule out COVID-19 in a patient who has symptoms consistent with COVID-19. Sensitivity of antigen tests may be further compromised if specimens are collected more than 5-7 days after the onset of symptoms or by staff with suboptimal training or supervision. A strategy for appropriate use of antigen tests for symptomatic individuals is shown on the left side of Figure 1 and includes the following considerations:
- Point-of-care tests, like antigen tests, should be used in favor of laboratory-based testing in settings where rapid results are needed to inform immediate decisions about patient care or infection control, or when access to molecular laboratory tests with acceptable turnaround time is inadequate.
- Symptomatic patients with positive antigen tests should be considered probable cases, placed in isolation, and reported to public health for investigation and contact tracing.
- Negative antigen tests in symptomatic patients should be followed-up with a second, different test for COVID-19. A molecular test is generally preferred as the second test. If molecular tests are not available, any FDA authorized test, including a second type of antigen test, may be used as the second test.
Figure 1. Strategy for use of SARS-CoV-2 antigen tests
Considerations for Use of Antigen Tests in Asymptomatic Patients
In situations where there is a low pre-test probability of disease, antigen tests have a high risk of false positive results that can lead to unnecessary clinical or infection control interventions. The EUA for all four available antigen tests were granted based on data supporting their use in symptomatic patients. The performance characteristics of antigen tests in asymptomatic people are not well understood. For these reasons it is not recommended that antigen tests be used for routine screening of people without symptoms or high-risk exposures.
Despite these limitations, there are settings where antigen tests have been embraced as a method of screening groups of individuals where there is a need for frequent testing and poor access to molecular testing. The FDA has provided guidance regarding such “off-label” use of antigen tests, in settings where highly sensitive tests are not feasible, or if turnaround times are prolonged:
“For congregate care settings, like nursing homes or similar settings, repeated use of rapid point of care testing may be superior for overall infection control compared to less frequent, highly sensitive tests with prolonged turnaround times.
If less sensitive tests, such as some rapid point-of-care tests, are used, healthcare providers should be aware of the performance of the tests and may want to consider different testing approaches, such as serial testing.”
The recommended strategy for using antigen tests in patients without symptoms in Wisconsin is described on the right side of Figure 1 (above).
- Asymptomatic individuals who have been in close contact with a person with COVID-19 should be tested with either a molecular or an antigen test. Persons recently exposed to COVID-19 that test positive by an antigen test should be considered as probable cases, requiring isolation and public health investigation.
- People who have been in close contact with a person with COVID-19 should be required to quarantine for 14 days. A negative test does not eliminate the requirement to quarantine for the full 14 days, which is the known incubation period of SARS-CoV-2.
- Positive antigen tests in asymptomatic people without recent contact with COVID-19 (i.e., asymptomatic screening) should be immediately tested again for COVID-19 by a different method. Organizations using antigen tests for asymptomatic screening should be prepared to immediately collect a second specimen for additional testing. Molecular testing is highly preferred for the greatest test accuracy. Specimens collected more than 48 hours after the first sample should be considered a new testing event and not confirmatory testing.
Reporting Requirements for SARS-CoV-2 Antigen Tests in Wisconsin
COVID-19 remains a reportable condition in Wisconsin, meaning that cases of COVID-19 are required to be reported to local public health departments within 24 hours. This requirement is most commonly satisfied through electronic laboratory reporting. While it is of interest for state and local public health to track the results of all positive and negative SARS-CoV-2 rapid antigen tests, current challenges related to data management and transfer may make universal reporting of point-of-care tests burdensome to providers using these tests and local health departments. At this time, DHS requests that only positive rapid SARS-CoV-2 antigen tests results be reported, as described below. General details about reporting requirements for COVID-19 can be found on the DHS COVID-19 Health Care Providers webpage, under “reporting and surveillance guidance.”
- At this time, except for nursing homes and skilled nursing facilities, only positive laboratory test results from antigen tests must be reported in Wisconsin. Negative results do not need to be reported to the local health departments or Wisconsin DHS. Patients being tested using an antigen test do not need to be reported until positive test results are received.
- Nursing homes and skilled nursing facilities that have received antigen testing supplies from the federal government are required to report results, both positive and negative, to the U.S. Department of Health and Human Services (HHS), in accordance with federal guidance.
- Mechanisms for federal reporting of positive and negative antigen tests by nursing homes and skilled nursing facilities are still in development at the national level. Facilities who wish to have DHS report to HHS on their behalf must report all antigen test results (positive and negative) electronically to the Wisconsin Electronic Disease Surveillance System (WEDSS). Reporting can occur through already established electronic laboratory reporting (ELR) connections, or by establishing a web-based laboratory reporting (WLR) connection. The Wisconsin State Laboratory of Hygiene (WSLH) recently presented an informational webinar on WLR reporting and has a request form to begin the sign-up process for WLR reporting.
- DHS guidance regarding reporting of molecular test results is unchanged. Both positive and negative laboratory results from a molecular amplification test (e.g. PCR, NAAT) must be reported.
Thank you for your attention to this important and evolving topic.
Ryan Westergaard, MD, PhD, MPH
Chief Medical Officer and State Epidemiologist for Communicable Diseases
Wisconsin Department of Health Services
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