What is an antigen test?
Antigen tests directly detect fragments of SARS-CoV-2 viral protein (as opposed to viral RNA detected by nucleic acid amplification tests [NAAT aka PCR tests]).
The main advantages of antigen tests are fast turnaround time, simple to perform point-of-care use, identification of current viral infection, and lower cost.
The main drawbacks are lower sensitivity (more false negatives) and intended use limited to individuals suspected of COVID-19 within 5-12 days of symptom onset (number of days varies by manufacturer).
Positive results in symptomatic individuals are likely to reflect an active infection, but negative tests are presumptive negative and depending on level of clinical concern may need to be confirmed with a NAAT/PCR.
A negative antigen test may not exclude infection and is of insufficient sensitivity to make decisions about discontinuing isolation.
Antigen tests are approved by the FDA for use on symptomatic individuals. No antigen test has yet been yet approved by the FDA for use on asymptomatic individuals.
If an antigen test is used outside the recommended window from symptom onset or to test asymptomatic individuals, false positive results can occur. Depending on the level of tolerance for potential false positive results, confirmatory NAAT may be indicated.
Rapid antigen tests for COVID-19 diagnosis in symptomatic individuals
- The U.S. Food and Drug Administration (FDA) maintains a list of in vitro diagnostic tests for COVID-19 that are approved under an Emergency Use Authorization (EUA). Only FDA EUA-approved viral diagnostic tests should be used. Current antigen tests with FDA EUA are approved as Clinical Laboratory Improvement Amendments (CLIA) of 1988 waived, point-of-care tests:
1) Quidel Sofia SARS Antigen FIA assay
2) BD Veritor System for Rapid Detection of SARS-CoV-2
3) LumiraDx SARS-CoV-2 Antigen Test
4) Abbott BinaxNOW COVID-19 Ag CARD
Performance of antigen tests
Sensitivity and specificity are measures of a test's ability to correctly classify a person as having a disease or not having a disease.
Sensitivity refers to a test's ability to designate an individual with disease as positive. A highly sensitive test means that there are few false negative results, and thus fewer cases of disease are missed.
Specificity refers to a test's ability to designate an individual who does not have a disease as negative. A highly specific test means that there are few false positive results.
Performance Characteristics of EUA-Approved Assays
Recommended use (in number of days since symptom onset)
| 5
| 5
| 7
| 12 |
|---|
| Positive percent agreement with PCR | 96.7% | 84.0% | 97.1% (95% CI: 85.1%-99.9% | 97.6% (95% CI: 91.6%-99.3%) |
|---|
| Specificity | 100%
| 100% | 98.5% | 97%
|
|---|
Antigen test processing specifications
- Current antigen tests detect the nucleocapsid protein of SARS-CoV-2 from a swab of a patient's nasal passage. Results are qualitative. A special machine may be needed.
- Dry swabs should be used for all tests. Transport medium should not be used. False positive test results have been reported when swabs are placed in viral transport medium prior to testing.
- Specimens should be tested as soon as possible after collection.
Interpretation of positive test results
- A positive test result in a symptomatic individual indicates that SARS-CoV-2 antigen was detected and that the individual is very likely infected and presumed to be contagious. Positive individuals should be isolated per California Department of Public Health guidance.
- A positive test result in an asymptomatic individual has the potential to be a false positive result. Asymptomatic individuals with a positive result should be considered to be cases and managed as such. In these situations, the individual with the positive test result should be isolated until confirmatory NAAT/PCR testing can be performed and results returned.
- Confirmatory nucleic acid testing following a positive antigen test may not be necessary when the pretest probability is high, especially if the person has a known exposure.
- False positive results are more likely to occur if the clinical suspicion and pre-test probability for COVID-19 is low.
Interpretation of negative test results
- Negative results for all antigen tests are considered presumptive negative.
- Asymptomatic individuals with presumptive negative tests in a congregate setting outbreak investigation with confirmed cases may need confirmatory NAAT/PCR testing.
- Symptomatic individuals with presumptive negative tests should be isolated until confirmatory NAAT/PCR testing can be performed and results returned.
When is it appropriate to use an antigen test?
- Antigen tests are most reliable when used on symptomatic individuals in populations with a high prevalence of disease. The goal is to quickly identify and isolate contagious individuals. A positive result would inform immediate, specific clinical, infection control, or public health action. In this setting, there is less concern about false positive results.
- Antigen tests are also useful in high prevalence serial testing environments (i.e. congregate living settings, high-risk essential workers, work settings, particularly anywhere in health care, and in outbreak investigations.
- Antigen tests are well suited for areas with little access to testing where access to frequent testing may be advantageous
- Results from antigen tests should always be interpreted in the context of the exposure history and clinical presentation.
Examples of scenarios in which SARS-CoV-2 antigen tests may reasonably be used:
- Symptomatic patients within the appropriate window for a given test and in settings with high rates of transmission.
- To rapidly triage patients in an Emergency Department or similar setting.
- Serialtesting and outbreak investigations in congregate living settings with confirmed cases, such as correctional facilities, long-term care facilities or other high-risk settings, particularly when PCR testing is limited or turnaround time is prolonged, e.g. >72 hours.
- Remote populations (e.g. rural hospitals, tribal nations, etc.) with limited access to testing.
- If antigen tests are used for asymptomatic testing (e.g. routine screening or pre-admission testing in congregate settings where there are no confirmed cases of COVID 19), repeat testing at set interval(s) can alleviate the lower sensitivity of antigen tests.
Testing facilities
Facilities that perform only CLIA-waived tests must possess either a CLIA Certificate of Waiver or a Certificate of Compliance. These locations may include long-term care facilities, hospitals, prisons, physician offices, urgent care clinics, outreach clinics, pharmacies and temporary patient care settings. Persons performing the point-of-care test must be trained to perform the test, but these sites have no routine regulatory testing oversight and no testing personnel requirements. If a large volume of tests is anticipated, such as in a skilled nursing facility, this may require full-time staff during weeks when response driven testing is performed.
Reporting of antigen test results
- For clinical care and for public health investigation and follow-up purposes, all patients with positive antigen test results should be considered true cases.
- However, for the purpose of surveillance, per the most recent updated interim CSTE case definition for COVID-19, positive antigen tests are considered presumptive, rather than confirmatory laboratory evidence of acute infection. Per the case definition, if "the patient has tested positive for SARS-CoV-2 by an antigen test of a respiratory secretion" they are considered probable cases for public health reporting purposes.
- Laboratories performing antigen tests are required by California law to report positive and negative results to public health agencies in the same way as other reportable test results.
- Non-laboratory settings conducting antigen tests must report positive and negative antigen test results to the local health department where the patient resides. Please contact your local health department for reporting instructions.
CDPH will update this guidance as more data become available.
Resources
- Food and Drug Administration. Performance characteristics of EUA-approved assays have been published in the "Instructions for Use" links on the FDA website.
- Council of State and Territorial Epidemiologists. Update to the standardized surveillance case definition and national notification for 2019 novel coronavirus disease (COVID-19), Interim-20-ID-02.
- Ramdas K, Darzi A, Jain S. 'Test, re-test, re-test': using inaccurate tests to greatly increase the accuracy of COVID-19 testing. Nat Med. 2020;26(6):810-811. doi:10.1038/s41591-020-0891-7
Originally Published on Septemeber 12, 2020