NEW YORK — A team led by scientists from Emory University has developed an approach that can evaluate the impact of common SARS-CoV-2 mutations on the accuracy of rapid antigen tests and used it to show that currently available tests are effective with past and current variants of the virus.
The findings were reported in this week's Cell.
As SARS-CoV-2 continues to evolve, concerns have grown over the performance of rapid antigen tests against variant mutations. To address this issue, a task force was established as part of the National Institutes of Health's Rapid Acceleration of Diagnostics Tech (RADx) program to assess the impact of mutations on COVID-19 diagnostic tests.
To that end, members of the RADx task force created a mammalian surface-display platform for the SARS-CoV-2 nucleocapsid protein, which is the target for the majority of antigen tests due to its high abundance in virions and infected individuals, and combined it with deep mutational scanning to evaluate how any single amino acid substitution in nucleocapsid could affect diagnostic antibody binding.
The approach, they wrote, "measures the effect of all possible nucleocapsid protein mutations on antibody binding in a single experiment and generates a complete, unique escape mutational profile for each antibody. Escape mutational profiles are characterized by distinct regions of high and low escape scores that clearly identify both the epitopes and the vulnerabilities of diagnostic antibodies to mutations within and distal to the epitope."
The group used their method to evaluate 17 antibodies used in commercially available antigen tests that have received Emergency Use Authorization from the US Food and Drug Administration including ones from Becton Dickinson, Quidel, Qorvo Biotechnologies, Clip Health, Quanterix, Ellume, ANP Technologies, MaximBio, and GenBody.
The investigators found that the rapid antigen tests are well positioned to detect the mutations found in previous and current variants of concern. "Furthermore, the data generated [in the study] contain binding measurements for all possible amino acid substitutions that may arise in future variants and thus are a valuable resource for the continued, accurate tracking of COVID-19 infections," the authors wrote.
"Accurate and efficient identification of infected individuals remains a critically important strategy for COVID-19 mitigation, and our study provides information about future SARS-CoV-2 mutations that may interfere with detection," Emory's Eric Ortlund, senior author of the study, said in a statement from the NIH. "The results outlined here can allow us to quickly adapt to the virus as new variants continue to emerge, representing an immediate clinical and public health impact."
The study, however, is not without its limitations. The researchers note that many SARS-CoV-2 variants of concern contain multiple mutations in the nucleocapsid protein and that their data cannot accurately predict escape mutations arising from multiple point mutations with synergistic effects. Additionally, the SARS-CoV-2 nucleocapsid protein contains several potential posttranslational modifications that may interfere with or be required for antibody binding, and the screen does not evaluate such modifications.