Characteristics Influencing Adherence to SARS-CoV-2 Serial Antigen Testing Following a Federal Safety Communication:...

Throughout the COVID-19 pandemic, regular population testing for SARS-CoV-2 was crucial for disease monitoring and management. Initially, reverse transcriptase-polymerase chain reaction tests were primarily used for identifying new cases, but their high cost and delayed results, combined with laboratory capacity and supply chain limitations, led to the adoption of antigen-detection rapid diagnostic tests (Ag-RDTs) at point-of-care locations. On August 11, 2022, the US Food and Drug Administration (FDA) issued a safety communication recommending serial Ag-RDT testing to reduce the risk of false-negative results from singular testing and combat disease spread, followed by a revision letter on November 1, 2022, to manufacturers to update their authorized product labeling.

This study evaluates adherence to serial testing using data from the Centers for Disease Control and Prevention (CDC) Increasing Community Access to Testing, Treatment, and Response (ICATT) program.

This national, retrospective cohort study analyzed ICATT program line-level testing records from August 12, 2022, to January 14, 2025. Patients were included if they had at least 1 Ag-RDT. Adherence was determined based on whether patients followed FDA guidance after a negative test. Multivariable logistic regression models were used to identify demographic features associated with adherence, with an expanded model to identify the impact of additional clinical variables. Rates of testing positive after an initial negative Ag-RDT were also calculated for ICATT pharmacy testing.

There were 2,189,464 patients included in the second-test adherence analysis, and 6813 included in the third-test adherence analysis. Less than 1% (20,290/2,189,464) of patients were adherent to the instructions to use a second Ag-RDT, and 98.2% (2,149,292/2,189,464) had no second test documented in ICATT and therefore were classified as nonadherent in this analysis. Second-test adherence was higher among Asian (adjusted odds ratio [AOR] 1.28, 95% CI 1.21-1.36) and Black (AOR 1.17, 95% CI 1.12-1.23) patients and lower among children (AOR 0.48, 95% CI 0.45-0.51). In the expanded model, recent COVID-19 contact increased adherence odds (AOR 1.87, 95% CI 1.64-2.13), whereas recent COVID-19 infection decreased them (AOR 0.66, 95% CI 0.56-0.76). Among patients with symptoms initially testing negative with an Ag-RDT, 24.9% (7310/29,315) tested positive on their second test, and 57.4% (4195/7310) of these episodes were adherent. For patients without symptoms, 4.2% (60/1435) tested positive on their third test after testing negative on their first 2 tests, with 60% (36/60) adherence.

This study is the first to evaluate adherence to the FDA instructions to perform serial Ag-RDTs. Overall, adherence was low among patients seeking testing at community sites. Recent COVID-19 exposure was associated with the highest odds of serial testing adherence. These insights can inform targeted public health strategies to improve adherence and reduce the risk of false-negative results from Ag-RDTs in future pandemics.