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

Abstract

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 (C _T ) 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 C _T 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.

Fig. 1.. Results of testing 8 commercially available rapid antigen tests against remnant clinical sample pools.

Each of eight commercially available rapid antigen tests (RATs) was tested using sequence-confirmed, serially diluted and quantified (N2 C_T CDC Assay and Quanterix Simoa SARS-CoV-2 N Protein Antigen Test) pools generated from remnant clinical samples (RCS) of the same variant. Panels A and B show each RAT’s limit of detection, which is the lowest antigen concentration (A) or highest C_T value (B) that was detected in five out of five replicates. When testing was repeated with independent RCS pools, or independent lots of tests, they are presented as separate data points.

Fig. 2.. Results of testing 2 commercially available rapid antigen tests against individual remnant clinical samples for Delta (A and B) and Omicron (C and D).

Sequence-verified residual mid turbinate samples from 75 individuals with Delta infection and 84 individuals with BA.1 infection underwent RT-PCR testing using the Xpert Xpress CoV-2/Flu/RSV plus & Xpert Xpress SARS-CoV-2 assays (Cepheid), protein quantification using the Simoa SARS-CoV-2 N Protein Antigen assay (Quanterix), and rapid antigen testing (QuickVue or Binax) according to the manufacturer’s instructions. Y-axes reflect natural log(n+1) transformed antigen concentration. Abbreviations: Cycle threshold (C_T)

Fig. 3.. Correlation between antigen concentration and C_T value for individual remnant clinical samples.

Sequence-verified residual mid turbinate samples from 163 individuals with Delta infection and 169 individuals with BA.1 infection underwent RT-PCR testing using the Xpert Xpress CoV-2/Flu/RSV plus & Xpert Xpress SARS-CoV-2 assays (Cepheid) and protein testing using the Simoa SARS-CoV-2 N Protein Antigen assay (Quanterix), according to the manufacturer’s instructions. Y-axes reflect natural log(n+1) transformed antigen concentration. The red circle signifies 41 Delta samples whose C_T values were above the assay detection limit and antigen concentrations were below the assay detection limit. Abbreviations: Cycle threshold (C_T).