Potential for False Positive Results with Antigen Tests for Rapid Detection of SARS-CoV-2 – Letter to Clinical Laboratory Staff and Health Care Providers

Authors: FDA

The U.S. Food and Drug Administration (FDA) is alerting clinical laboratory staff and health care providers that false positive results can occur with antigen tests, including when users do not follow the instructions for use of antigen tests for the rapid detection of SARS-CoV-2. Generally, antigen tests are indicated for the qualitative detection of SARS-CoV-2 antigens in authorized specimen types collected from individuals who are suspected of COVID-19 by their healthcare provider within a certain number of days of symptom onset. The FDA is aware of reports of false positive results associated with antigen tests used in nursing homes and other settings and continues to monitor and evaluate these reports and other available information about device safety and performance.

The FDA reminds clinical laboratory staff and health care providers about the risk of false positive results with all laboratory tests. Laboratories should expect some false positive results to occur even when very accurate tests are used for screening large populations with a low prevalence of infection. Health care providers and clinical laboratory staff can help ensure accurate reporting of test results by following the authorized instructions for use of a test and key steps in the testing process as recommended by the Centers for Disease Control and Prevention (CDC), including routine follow-up testing (reflex testing) with a molecular assay when appropriate, and by considering the expected occurrence of false positive results when interpreting test results in their patient populations.  

For More Information: https://www.fda.gov/medical-devices/letters-health-care-providers/potential-false-positive-results-antigen-tests-rapid-detection-sars-cov-2-letter-clinical-laboratory

Antigen and Molecular Tests

Diagnostic tests are used to detect current, active infections of the SARS-CoV-2 virus. Diagnostic tests can be antigen based (“rapid antigen” tests), which look for protein markers on the outside of the virus, or they can be molecular based (including PCR, LAMP, CRISPR), which look for viral genomic material specific to SARS-CoV-2. Molecular based tests that amplify genetic material are also called nucleic acid amplification tests (NAAT). 

More about antigen and molecular tests:

For More Information: https://www.centerforhealthsecurity.org/covid-19TestingToolkit/testing-basics/types-of-COVID-19-tests/antigen-and-molecular-tests.html

Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses

Authors: Ian W. Pray, PhD1,2,3,*; Laura Ford, PhD1,2,*; Devlin Cole, MD3,4; Christine Lee, PhD1,5; John Paul Bigouette, PhD1,2; Glen R. Abedi, MPH1; Dena Bushman, MSN, MPH1,2; Miranda J. Delahoy, PhD1,2; Dustin Currie, PhD1,2; Blake Cherney, MS1; Marie Kirby, PhD1; Geroncio Fajardo, MD1; Motria Caudill, PhD1,6; Kimberly Langolf, MS7; Juliana Kahrs, MS7; Patrick Kelly, MD4,8; Collin Pitts, MD4,8; Ailam Lim, PhD9; Nicole Aulik, PhD9; Azaibi Tamin, PhD1; Jennifer L. Harcourt, PhD1; Krista Queen, PhD1; Jing Zhang, PhD1; Brett Whitaker, PhD1; Hannah Browne1; Magdalena Medrzycki, PhD1; Patricia Shewmaker, PhD1; Jennifer Folster, PhD1; Bettina Bankamp, PhD1; Michael D. Bowen, PhD1; Natalie J. Thornburg, PhD1; Kimberly Goffard, MBA10; Brandi Limbago, PhD1; Allen Bateman, PhD7,11; Jacqueline E. Tate, PhD1; Douglas Gieryn10; Hannah L. Kirking, MD1; Ryan Westergaard, MD, PhD3,4; Marie Killerby, VetMB1; CDC COVID-19 Surge Laboratory Group (View author affiliations)

Summary

What is already known about this topic?

Antigen tests for SARS-CoV-2 are inexpensive and can return results within 15 minutes, but test performance data in asymptomatic and symptomatic persons are limited.

What is added by this report?

Compared with real-time reverse transcription–polymerase chain reaction (RT-PCR) testing, the Sofia antigen test had a sensitivity of 80.0% and specificity of 98.9% among symptomatic persons; accuracy was lower (sensitivity 41.2% and specificity 98.4%) when used for screening of asymptomatic persons.

What are the implications for public health practice?

To account for reduced antigen test accuracy, confirmatory testing with a nucleic acid amplification test (e.g., RT-PCR) should be considered after negative antigen test results in symptomatic persons and positive antigen test results in asymptomatic persons.

For More Information: https://www.cdc.gov/mmwr/volumes/69/wr/mm695152a3.htm

Interim Guidance for Antigen Testing for SARS-CoV-2

Authors: CDC

Summary of Recent Changes

Updates as of May 13, 2021

  • Updated guidance based on new published studies on antigen test performance.
  • Clarification about which NAATs should be used for confirmatory testing.
  • Considerations for people who have had previous SARS-CoV-2 infections and those who have been fully vaccinated.
  • Two new antigen testing algorithms, one for congregate living settings, and one for community settings.
  • Updates to testing suggestions for fully vaccinated, asymptomatic people.
    View Previous Updates

Key Points

  • This interim guidance is intended for healthcare providers who order antigen tests, receive antigen test results, or perform point-of-care testing, as well as for laboratory professionals who perform antigen testing in a laboratory setting or at the point of care and report those results.
  • The purpose of this interim technical guidance is to support effective clinical and public health use of antigen tests for different testing situations.
  • This guidance applies to all clinical and consumer uses of antigen tests and is not specific to any particular age group.
  • This guidance incorporates considerations for fully vaccinated people and should be used in conjunction with CDC’s Interim Public Health Recommendations for Fully Vaccinated People.

For More Information: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html