Impaired detection of omicron by SARS-CoV-2 rapid antigen tests

Abstract

Since autumn 2020, rapid antigen tests (RATs) have been implemented in several countries as an important pillar of the national testing strategy to rapidly screen for infections on site during the SARS-CoV-2 pandemic. The current surge in infection rates around the globe is driven by the variant of concern (VoC) omicron (B.1.1.529). Here, we evaluated the performance of nine SARS-CoV-2 RATs in a single-centre laboratory study. We examined a total of 115 SARS-CoV-2 PCR-negative and 166 SARS-CoV-2 PCR-positive respiratory swab samples (101 omicron, 65 delta (B.1.617.2)) collected from October 2021 until January 2022 as well as cell culture-expanded clinical isolates of both VoCs. In an assessment of the analytical sensitivity in clinical specimen, the 50% limit of detection (LoD50) ranged from 1.77 × 106 to 7.03 × 107 RNA copies subjected to the RAT for omicron compared to 1.32 × 105 to 2.05 × 106 for delta. To score positive in these point-of-care tests, up to 10-fold (LoD50) or 101-fold (LoD95) higher virus loads were required for omicron- compared to delta-containing samples. The rates of true positive test results for omicron samples in the highest virus load category (Ct values < 25) ranged between 31.4 and 77.8%, while they dropped to 0–8.3% for samples with intermediate Ct values (25–30). Of note, testing of expanded virus stocks suggested a comparable RAT sensitivity of both VoCs, questioning the predictive value of this type of in vitro-studies for clinical performance. Given their importance for national test strategies in the current omicron wave, awareness must be increased for the reduced detection rate of omicron infections by RATs and a short list of suitable RATs that fulfill the minimal requirements of performance should be rapidly disclosed.

Analytical performance of rapid antigen tests for the detection of SARS-CoV-2 during widespread circulation of the Omicron variant

“…There has been insufficient investigation into the diagnostic performance of antigen testing for the Omicron variant. Osterman et al demonstrated that nine SARS-CoV-2 antigen tests commercially available in Europe showed decreased sensitivities for the Omicron variant [12].…”

SARS-CoV-2: An Overview of the Genetic Profile and Vaccine Effectiveness of the Five Variants of Concern

“…If the virus is rapidly evolving, tests targeting a single epitope have a lower sensitivity and, consequently, a lower accuracy of the results [ 120 ]. Thus, in the case of the Omicron variant, it has been observed that N mutations can determine the accuracy of currently approved commercial antigen tests [ 121 ].…”

Performance study of a point-of-care antigen test during the SARS-CoV-2 Delta to Omicron variant transition in the USA

“…Other studies have also reported reduced sensitivity for the Omicron variant with some antigen tests [10, 11]. The reduced sensitivity reported did not appear to be due to reduced viral load in samples,[11] and a study of different sampling methods noted that nasal swab samples had higher sensitivity compared with oral (cheek or throat) swabs, suggesting that this common sampling method is the most effective for detecting the Omicron variant [12].…”

“…Preliminary results from the US National Institutes of Health RADx program, which studied the performance of antigen tests using patient samples containing the Omicron variant, suggested that these tests detect the Omicron variant but may have reduced sensitivity [9]. Other studies have also reported reduced sensitivity for the Omicron variant with some antigen tests [10,11]. The reduced sensitivity reported did not appear to be due to reduced viral load in samples, [11] and a study of different sampling methods noted that nasal swab samples had higher sensitivity compared with oral (cheek or throat) swabs, suggesting that this common sampling method is the most effective for detecting the Omicron variant [12].…”