As new variants of the SARS-CoV-2 virus continue to emerge, concerns have been raised about the performance of rapid antigen tests. However, commercially available rapid antigen tests can detect past and present variants of concern, according to a recent study published in Cell.
The Emory University researchers who conducted the study used a method called deep mutational scanning (DMS) to simultaneously evaluate how any single amino acid substitution in the nucleocapsid (N) protein SARS-CoV-2 could affect diagnostic antibody binding.
They generated a library of N protein variations, which includes nearly 8,000 single amino acid substitutions -- representing more than 99.5% of all possible mutations -- and evaluated their interaction with 17 different diagnostic antibodies used in 11 commercially available rapid antigen tests, the National Institutes of Health (NIH) said in a statement. The NIH funded the Cell study through its Rapid Acceleration of Diagnostics (RADx) Tech program.
The study adds to growing evidence that rapid antigen tests remain accurate for detecting variants of SARS-CoV-2.
In August, a team at the University of Washington, in cooperation with University of Nevada, concluded that two rapid antigen tests -- SCoV-2 Ag Detect Rapid Self-Test (InBios International) and Binax Now COVID-19 Ag Card (Abbott Laboratories) -- had consistent analytical and clinical accuracy across three phases of circulating forms of the SARS-CoV-2 variants.
The more recent study has shown that commercially available rapid antigen tests, which have obtained Emergency Use Authorizations from the U.S. Food and Drug Administration, can also identify potential mutations that may impact test performance in the future, the NIH said.
"Based on our findings, none of the major past and present SARS-CoV-2 variants of concern contain mutations that would affect the capability of current rapid antigen tests to detect antibodies," Filipp Frank, the first author of the study and assistant professor of biochemistry at Emory University, said in a statement. He further said that the findings could be used to predict a test's performance against future variants.
"We evaluated binding of antibodies from 11 commercial antigen tests ... to all possible mutations in the nucleocapsid protein," the researchers wrote in Cell. "For each antibody tested, the results provide a comprehensive list of antigen mutations with the potential to evade detection in the associated diagnostic test."
The researchers added that their approach provides a mutational profile reminiscent of a fingerprint of the antibody on the antigen. "These fingerprints are highly valuable in the evaluation of antibodies and other detection reagents, such as nanobodies or DNA aptamers used in a diagnostic test, regarding their ability to detect variants of a rapidly mutating viral antigen," they wrote.
Despite the promising findings, the Emory University researchers noted some limitations with their study. The DMS library contained only single mutations, meaning that the data may not predict escape mutations from multiple point mutations with synergistic effects, the researchers said.
"Rapid antigen tests remain an important COVID-19 mitigation tool, and it is essential to ensure that these tests can detect the SARS-CoV-2 virus as it continues to evolve," Bruce Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and lead for the RADx Tech program at the NIH, said in a statement. "Considering the endless cycle of new variants, the data from this study will be useful for years to come."
The NIH established the RADx Tech program in 2020 to speed the development, validation, and commercialization of innovative point-of-care, home-based, and clinical laboratory tests that can directly detect the SARS-CoV-2 virus.