Sensitivity of Rapid Antigen Tests Against SARS-CoV-2 Omicron and Delta Variants

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (CT) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using CT value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution. ### Competing Interest Statement ALG reports contract testing from Abbott, Cepheid, Novavax, Pfizer, Janssen, and Hologic, and research support from Gilead and Merck, outside of the described work. The other authors have declared that no conflict of interest exists. ### Funding Statement This work was supported by the National Institute of Biomedical Imaging and Bioengineering under the Atlanta Center for Microsystems Engineered Point-of-Care Technologies (ACME POCT). This work was supported by the NIBIB at the NIH under awards 3U54 EB027690-03S1, 3U54 EB027690-03S2, 3U54 EB027690-04S1 and the National Center for Advancing Translational Sciences of the NIH under award UL1TR002378. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Emory Institutional Review Board and Childrens Healthcare of Atlanta (IRB00001082). Written informed consent was received prior to participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript and supplementary data file.