Widely utilized SARS-CoV-2 rapid antigen detection tests continue to perform as expected despite Omicron mutations

By Shanet Susan AlexReviewed by Danielle Ellis, B.Sc.Feb 22 2022

A recent study posted to the medRxiv* preprint server evaluated the performance of three at-home coronavirus disease 2019 (COVID-19) rapid antigen tests commonly used in the United States (US) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

SARS-CoV-2 rapid antigen detection tests (RADTs) are now widely used in the US as they can be self-administered, involves no or little equipment, and deliver results within 15 minutes. Moreover, since these tests can be used at the point of treatment with the beginning of SARS-CoV-2 symptoms or before gatherings, RADTs serve a vital role in relaxing the stringent COVID-19 associated restrictions in society. However, these tests must be reassessed regularly to ensure that test performance does not deteriorate as the virus undergoes mutations. 

Most of the RADTs target the SARS-CoV-2 nucleoprotein (N) protein, and the Omicron variant possesses multiple previously unidentified N protein mutations. However, the impact of the Omicron's mutations on the efficiency of the RADTs remains unclear.

About the study

In the present study, the researchers assessed the influence of mutations in Omicron on the efficiency of the three widely used over the counter (OTC) at-home COVID-19 rapid antigen testing kits: 1) iHealth COVID-19 Antigen Rapid Test, 2) ACON Laboratories FlowFlex COVID-19 Antigen Home Test, and 3) Abbott BinaxNOW COVID-19 Antigen Card. The scientists evaluated the performance of the three SARS-CoV-2 RADTs on 30 Omicron and Delta variant samples, respectively, with a broad range of viral loads, and the Delta sample set served as a comparator for the study.

Except for nine Delta samples collected between August and November 2021, the researchers procured 30 samples positive for the Omicron and the Delta variants from patients seeking medical care at the Massachusetts General Hospital between November 30 and December 27, 2021.

The samples were obtained from the anterior nares of the patients and analyzed using the Roche cobas SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Further, the SARS-CoV-2 variant was identified through the TaqPath COVID-19 Combo Kit. 

Study findings

The results indicate that all three RADTs evaluated had similar analytic sensitivity for detecting the SARS-CoV-2 Omicron variant compared to the Delta variant. However, there were variances in performance between the three assays.

Across an overlap of eight PCR cycles, the Abbott BinaxNOW COVID-19 RADT exhibited SARS-CoV-2 positive and negative results, equivalent to a 256-times variation in the quantity of virus contained in a sample, assuming a 100% reaction efficiency. In contrast, the range of overlap for the FlowFlex RADT was restricted to three PCR cycles, which represents an eight-times variation in SARS-CoV-2 concentration in a sample.

None of the RADTs detected samples with a cycle threshold (Ct) value of 27.5 or more for the SARS-CoV-2 envelope (E) gene target demonstrated by the Roche cobas RT-PCR assay.

The SARS-CoV-2 variant type did not predict the chances of test positivity after controlling for RADTs and Ct values in the multivariate analyses. Nonetheless, the Abbott BinaxNOW COVID-19 Antigen Card demonstrated an 89% lower chance of being positive for Omicron samples versus the iHealth COVID-19 RADT. Further, no statistically relevant variations in the odds of being positive were observed among the FlowFlex and the iHealth COVID-19 RADTs.

Conclusions

The study findings show despite the additional number of mutations in the Omicron N, the three commonly used RADTs targeting SARS-CoV-2 N protein for self-testing of COVID-19 in the US remained efficient in detecting the variant. Although the analytic sensitivity of RADTs did not change across Omicron and Delta variant containing samples, there were variances in performance based on assay type. Nevertheless, given the limited sample size of the current study, these findings should be construed with caution and should be investigated in future studies.

Further, the team reported an insignificant trend of lower detection of the SARS-CoV-2 Omicron variant with the Abbott BinaxNOW COVID-19 RADT, which they had also observed in a previous investigation employing a different sample set.

According to the authors, this is the first study independently evaluating the performance of the iHealth COVID-19 test against the Omicron variant. Although non-significant, higher sensitivity and better differentiation among SARS-CoV-2-positive and negative results were demonstrated by the iHealth COVID-19 test compared to the FlowFlex RADT.

Since the rationale for the overlap of viral loads in the Abbott BinaxNOW and FlowFlex COVID-19 RADTs was unknown, further investigations are required to determine if these variations are replicable in other settings. 

Overall, the study establishes a baseline for COVID-19 RADTs comparison with the future SARS-CoV-2 variants and offers some assurance that the at-home COVID-19 testing would function as predicted compared to previous waves of the SARS-CoV-2 pandemic.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.