Impact of SARS-CoV-2 Omicron on Rapid Antigen Testing Developed for Early-Pandemic SARS-CoV-2 Variants

Abstract

Rapid antigen tests (RATs) are widely used for point-of-care or self-testing to identify SARS-CoV-2 (SCoV2), but currently circulating Omicron variants may impair detection. In this study, we prospectively evaluated the Roche-SARS-CoV-2-Antigen and Acon-FlowFlex-SARS-CoV-2-Antigen in 150 consecutively collected nasopharyngeal patient swabs (50 SCoV2 RNA undetectable; 100 SCoV2 Omicron BA.1). Omicron BA.1 results were compared to 92 Ct-matched early-pandemic SCoV2 variants (B.1.160 and B.1.177), to 100 Omicron BA.2 positive and to 100 Omicron BA.5 positive samples. For Omicron BA.1, Roche-SARS-CoV-2-Antigen detected 87% of samples having Ct-values <29 reflecting 3.6% lower rates compared to B.1.160 and B.1.177. Acon-FlowFlex-SARS-CoV-2-Antigen was less affected and detected 90% of Omicron BA.1 with Ct-values <29. Omicron BA.2 and BA.5 detection rates were significantly reduced by 20% and 10%, respectively, for the Roche-SARS-CoV-2-Antigen in samples with Ct-values <29 but remained similar for Acon-FlowFlex-SARS-CoV-2-Antigen. RATs need to be continuously evaluated as new SCoV2-variants emerge. Spreading of Omicron-BA.2, and the recently emerged Omicron BA.5 variant, may not only result from escape from postvaccine or postinfection immunity, but also from false-negative RATs misguiding point-of-care and self-testing decisions at times of restricted molecular testing. IMPORTANCE Antigen tests are widely used for rapid identification of SCoV2-positive cases and their increased risk of transmission. At present, there are several FDA- and CE-cleared tests available in North America and Europe. However, their diagnostic performance has been evaluated with early-pandemic variants. This study provides evidence that variation within the nucleocapsid protein as seen in recently emerged and now globally spreading Omicron BA.2 and BA.5 variants significantly impairs detection rates of widely used antigen tests. Consequently, antigen tests need to be reevaluated when new pandemic SCoV2 variants emerge and start to predominate globally.

Keywords: BA.2; BA.5; COVID-19; Omicron; RAT; SARS-CoV-2; rapid antigen tests; severe acute respiratory syndrome coronavirus 2; variant.

FIG 1

Comparison of the cumulated sensitivity for Omicron detection with the Roche-SARS-CoV-2 and the Acon-FlowFlex-SARS-CoV-2 rapid antigen tests. Cumulative sensitivity of the Roche-SARS-CoV-2 and the Acon-FlowFlex-SARS-CoV-2 RATs for Omicron BA.1 detection were compared in Ct-matched UTM samples with early-pandemic SCoV2 variants (B.1.160 and B.1.177; n = 92) (1), Omicron BA.2 and Omicron BA.5 (n = 100). SCoV2 loads were determined using the cobas SARS-CoV-2 test on the cobas6800 platform (Roche). A. Cumulated sensitivity of the Roche-SARS-CoV-2 (BA.1) and the Roche-SARS-CoV-2(B.1.160 and B.1.177) (n = 92; median, 25th and 75th percentile; Mann-Whitney-U test). B. Cumulated sensitivity of the Roche-SARS-CoV-2-Antigen (BA.1) and the Acon-FlowFlex-SARS-CoV-2 (BA.1) (n = 92; median, 25th and 75th percentile; Mann-Whitney-U test). C. Cumulated sensitivity of the Roche-SARS-CoV-2 and the Acon-FlowFlex-SARS-CoV-2 for Omicron BA.1, Omicron BA.2 and Omicron BA.5 (n = 100; median, 25th and 75th percentile; Mann-Whitney-U test). D. Receiver operating characteristic analysis (ROC) curves for the Roche-SARS-CoV-2 and the Acon-FlowFlex-SARS-CoV-2 for the different SCoV2 variants stratified by SCoV2 RNA loads.