Antigen Testing Recommendations

 Interim COVID-19 Antigen Testing Recommendations
Virginia Department of Health
December 11, 2020

 

Introduction and Background

Multiple testing modalities exist for the diagnosis of SARS-CoV-2 infection. Molecular testing (e.g., PCR) has been widely used for diagnostic purposes since the pandemic began and is considered the current “gold standard” by the Centers for Disease Control and Prevention (CDC).  The Virginia Department of Health (VDH) recommends that the most sensitive and specific test be used for COVID-19 testing where possible.  However, the need for faster results, supply chain challenges, and molecular testing capacity issues has necessitated diversifying testing modalities to include the use of COVID-19 point of care (POC) antigen tests as well.

This document provides VDH’s current recommendations regarding the use, evaluation, and interpretation of COVID-19 antigen tests.  As of December 11, 2020, eight antigen tests have Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA).  Seven of these tests are available as point-of-care testing platforms.  This document also contains considerations for the “off-label” use of antigen tests under certain circumstances.

While reporting of antigen test results to VDH is mandated, the interim recommendations noted for the clinical use and interpretation of antigen tests are not mandates or requirements.  Providers should utilize their clinical judgment as appropriate to make the best clinical decision for their patients.  However, the clinical guidance provided in this document reflects subject matter input and consensus from VDH, the Governor’s Testing Advisory Council, and follows closely a document issued by the North Carolina Department of Health and Human Services on October 8, 2020, which VDH would also like to acknowledge.  As additional information and data about antigen testing become available, it is possible these recommendations will change.

Use of Antigen Tests

COVID-19 antigen tests are designed for the rapid diagnosis of active infection by detecting proteins on the surface of the SARS-CoV-2 virus (the virus that causes COVID-19) via nasal swabs or similar clinical specimens.  After specimen collection, point-of-care antigen tests take approximately 15 minutes to finalize a result.

Antigen tests are generally less sensitive than PCR-based methods, and their clinical performance depends on the circumstances in which they are used.  Because of the lower sensitivity, false negative antigen test results are possible and testing is most accurate when there is a high pre-test probability of SARS-CoV-2 infection (e.g., high prevalence of infection in the community, a patient whose clinical picture is consistent with COVID-19, etc.).  In addition, viral carriage is highest early in infection; therefore, antigen tests are more likely to detect a true positive early in infection. Thus far, all performance data have only been in symptomatic patients early in the course of infection.

Most antigen tests are meant to be used within 5–7 days after symptom onset, though specific tests such as the LumiraDx SARS-CoV-2 Ag Test allow for testing up to 12 days after symptom onset.  It is important for the healthcare provider to refer to the manufacturer’s instructions or the FDA EUA letter for the appropriate time window for the test being used.

The CDC has released general guidance for antigen testing for SARS-CoV-2.  To address one of the highest risk locations for transmission of COVID-19, the CDC also developed considerations for use and interpretation of SARS-CoV-2 antigen testing results in nursing homes, which includes testing information depending on the clinical presentation and the epidemiologic context.

While the primary use of antigen testing should be geared towards testing of symptomatic individuals, VDH acknowledges that antigen tests are also being used off-label for testing of asymptomatic individuals such as staff in long-term care facilities or for screening in certain work, educational, or other community settings.  This off-label testing is occurring even though there are limited test performance data in asymptomatic individuals.  Providers conducting testing on asymptomatic populations must be aware of the potential for a presumed false positive result with an antigen test that will necessitate confirmation with a subsequent PCR test.  Please see the table on the following page for full guidance on the interpretation and follow-up of antigen tests results.

Examples of populations or circumstances where antigen testing could be considered

  • Symptomatic individual(s) in whom COVID-19 is suspected, particularly within seven days of symptom onset, though this time window may be extended based on the specific test manufacturer’s instructions.
  • Asymptomatic individual(s) with close contact to someone with known COVID-19. Testing should occur 5 days or more after the last known exposure.  If an individual is suspected of having COVID-19 based on exposure, an antigen test can be performed.
  • Symptomatic and asymptomatic residents and staff in congregate settings (e.g., nursing homes or similar settings) where less frequent, highly sensitive tests such as PCR tests are not available or subject to prolonged turnaround times (> 48 hours).
    • As part of an outbreak response in a nursing home, serial testing (antigen or PCR) should be performed every 3-7 days for all residents and healthcare personnel until no new cases are identified in a 14-day period. Antigen tests should not be used to determine the duration of Transmission-based Precautions or when healthcare personnel can return to work.
    • Per CMS regulations, routine serial testing (using antigen or PCR) of nursing home staff is required. This may be considered in other congregate settings.
  • Asymptomatic people who are NOT close contacts to a known COVID-19 case, in settings where a highly sensitive test is not feasible or turnaround times are excessive.
    • This screening for disease may allow for earlier detection of COVID-19 so that prompt public health intervention can be taken.
    • The FDA has commented on this issue.
  • Asymptomatic individuals who participated in higher-risk activities in which they could not physically distance as needed (e.g., travel, attending large social or mass gatherings, or being in crowded indoor settings).

Evaluating Antigen Test Results

Results should be interpreted with consideration of the pre-test probability of infection, including the patient’s recent exposures and presence/absence of clinical signs and symptoms consistent with COVID-19. The table below summarizes the interpretation of antigen test results. Nursing homes should follow Considerations for Use of SARS-CoV-2 Antigen Testing in Nursing Homes for specific information on infection prevention and control measures, including cohorting.

Table. Antigen test result interpretation for symptomatic and asymptomatic persons

Test Result  Person being Tested
 Symptomatic Person

 

(test as close to symptom onset as possible and as recommended by manufacturer)

 Asymptomatic Person with Close Contact# to a known COVID-19 case  Asymptomatic Person without Close Contact# to a known COVID-19 case
Positive •   Current infection

•   Prompt isolation until no longer contagious by symptom-based strategy

•   Current infection

•   Prompt isolation until no longer contagious by time-based strategy

•   Presumptive current infection

•   Prompt isolation while awaiting confirmatory test result

•   Confirm positive result with a PCR test done in a high-complexity CLIA-certified laboratory+*

•   Patients with positive confirmatory test should isolate until no longer contagious by time-based strategy

Negative •   No antigens were detected

•   Confirm negative antigen result with a PCR test done in a high-complexity CLIA-certified laboratory+

•   Prompt isolation while awaiting confirmatory test result

•   No antigens were detected

• Close contacts who test negative must still complete 14 days of quarantine^

•   Obtain COVID-19 PCR test if person develops symptoms

•   No antigens were detected

•   No additional case follow-up necessary

•   Reinforce prevention measures

#Close contact is defined as being within six feet of someone known to have COVID-19 for a total of 15 minutes or longer over a 24-hour period, or having exposure to respiratory secretions from an infected person (e.g., being coughed or sneezed on, sharing a drinking glass or utensils, kissing), starting from two days before the person became sick (or two days before specimen collection if asymptomatic) until the person was isolated.

^ VDH and CDC continue to recommend a 14-day quarantine period as the safest option. If the person cannot stay home for the full 14 days after exposure and does not have symptoms, the person may end quarantine earlier. Counting the date of last exposure as Day 0, the person may leave home after Day 10 without testing, or after Day 7 with a negative PCR or antigen test performed on or after Day 5. If the person does not stay home for the recommended 14 days, the person should continue monitoring for symptoms and follow all other recommendations (e.g., wear a mask, watch their distance, and wash hands often) for the full 14-day period after the last exposure.

*A positive antigen test result in an asymptomatic, unexposed individual should be immediately followed by a PCR test in a high-complexity CLIA-certified laboratory to verify the positive result. This follow-up specimen should be collected within 24 hours of the original test, if possible, and no more than 48 hours after the antigen test. Specimens collected more than 48 hours after the initial test may lead to discordant results. If the confirmatory PCR is negative on an appropriate specimen collected in the proper time frame, and the individual has remained asymptomatic, the antigen test would be considered a false positive and the individual not counted as a COVID-19 case.

+While multiple specimen types may be acceptable, if possible, confirmatory tests should be performed using specimens with evidence of the most sensitivity, such as nasopharyngeal or mid-turbinate swabs.

Clinical management of patients with a positive antigen test should be the same as for patients with a positive PCR test, beginning with prompt isolation.  Further public health actions including case investigation and contact tracing should be initiated in coordination with the local health department.

Currently Available POC Antigen Tests

As of December 11, 2020, the following POC antigen tests have an EUA from FDA:

  • Abbott – BinaxNOW COVID-19 Ag Card
  • Access Bio, Inc. – CareStart COVID-19 Antigen test
  • Becton, Dickinson and Company (BD) – BD Veritor System for Rapid Detection of SARS-CoV-2
  • Luminostics, Inc. – Clip COVID Rapid Antigen Test
  • LumiraDx UK Ltd. – LumiraDx SARS-CoV-2 Ag Test
  • Quidel Corporation – Sofia SARS Antigen FIA
  • Quidel Corporation – Sofia 2 Flu + SARS Antigen FIA

Reporting Antigen Test Results

All positive and negative antigen results from diagnostic or screening testing must be reported to VDH within 24 hours. The requirements and methods of reporting for antigen tests are the same as for molecular tests (e.g., PCR). Laboratories and testing sites are required to report electronically.

VDH has developed a reporting portal for point-of-care (POC) COVID-19 test results. This portal can assist testing sites that lack Electronic Laboratory Reporting (ELR) capability in meeting the requirement of the CARES Act to report every diagnostic and screening test (e.g., molecular, antigen, antibody) performed to detect SARS-CoV-2 or to diagnose a possible case of COVID-19. This portal allows for the rapid entry of person-level test results for positive and negative results and provides the ability to enter aggregate negative results as necessary for high-volume testing sites.

Sites conducting POC testing will need to register first to utilize the reporting portal. During this one-time registration, facilities will provide site information and select the type(s) of testing equipment utilized.  When reporting results, sites will need to provide individual patient information, including demographic information, and the test result.  Additionally, specific questions requested by the U.S. Department of Health and Human Services (HHS) can be answered if the information is known.

If a false positive or false negative antigen test result is found, VDH recommends that the findings be reported to FDA and the test manufacturer.

References

12/11/2020: Revision to document

  • Removed “rapid” because FDA has authorized laboratory-based antigen tests.
  • Updated the number of antigen tests and POC antigen tests currently available as of December 10, 2020.
  • Included “asymptomatic individuals who participated in higher-risk activities in which they could not physically distance as needed (e.g., travel, attending large social or mass gatherings, or being in crowded indoor settings)” in populations or circumstances where antigen testing could be considered.
  • Changed the period when asymptomatic close contacts should be tested from “approximately 1 week” to “5 days or more” after the date of last contact.
  • Changed the duration of quarantine to include two alternatives if the person is not able to stay home for the recommended 14 days after last exposure and has no symptoms as noted in the added footnote to Table. These options to end quarantine early are “after Day 10 without testing,” or “after Day 7 with a negative PCR or antigen test performed on or after Day 5.” If these alternatives are used, the person should still monitor symptoms and follow other public health recommendations for the full 14-day period.
  • Added 2 CDC references: Interim Guidance for Antigen Testing and Overview of Testing for SARS-CoV-2 (COVID-19).

11/4/2020: Revision to Table on page 2

  • In the column concerning an asymptomatic person who is antigen test positive and a close contact to a known COVID-19 case, the person is considered to be currently infected and contagious until released from isolation using a time-based strategy. The previous version noted a symptom-based strategy.
  • In the column concerning an asymptomatic person with no known COVID-19 exposure, but with a positive antigen test and confirmatory positive PCR test, the person is considered contagious until released from isolation using a time-based strategy. The previous version noted a symptom-based strategy.