Analytical Sensitivity of Eight Different SARS-CoV-2 Antigen-Detecting Rapid Tests for Omicron-BA.1 Variant

Abstract

Sensitivity for detecting Omicron-BA.1 shows high heterogenicity between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. Analytical and retrospective testing is a proxy and timely solution to generate rapid performance data, but it is not a replacement for clinical evaluations, which are urgently needed. Biological and technical reasons for detection failure by some Ag-RDTs need to be further investigated.

Decreased Sensitivity of Rapid Antigen Test Is Associated with a Lower Viral Load of Omicron than Delta SARS-CoV-2 Variant

“…At the time of diagnosis, our results show that the RDT’s sensitivity is decreased for Omicron variant compared to Delta variant, associated with a lower VL in nasopharyngeal samples of individuals rather than an alteration of the N-antigen recognition by the RDT. These results are in accordance with other studies that explored different available RDTs in patients infected by these two VOCs ( 4 , 5 ). Moreover, a lower VL of the Omicron variant was also supported by two studies based on infectious or genomic VLs ( 6 , 7 ).…”

Variable detection of Omicron-BA.1 and -BA.2 by SARS-CoV-2 rapid antigen tests

“…The sensitivity of RATs has been demonstrated to underlie a huge inter-test variability, ranging from 0 to 98.6% [3][4][5][6]. Importantly, RATs can also show pronounced differences in intra-assay comparisons of sensitivity for the detection of different variants of concern (VoCs) of SARS-CoV-2 [7][8][9][10][11]. Thus, it is important to re-evaluate commercially available RATs on a regular basis by independent laboratories to identify those that still fulfill the WHO performance criteria once a new VoC is starting to dominate the pandemic.…”

“…We and others have examined the sensitivity of a number of RATs to detect different VoCs documenting a highly variable inter-and intra-test performance [4,[6][7][8][9][10][12][13][14][15][16][17][18][19][20]. With the appearance of the Omicron sublineages BA.1 and BA.2 in late 2021 and early 2022 [21,22], more mutations in the spike protein, but also in the nucleocapsid protein have been reported [23,24].…”

“…To score positive in these pointof-care tests, up to 22-fold (LoD50) or 68-fold (LoD95) higher viral loads were required for the worst performing compared to the best performing RAT. The rates of true-positive test results for these Omicron subvariant-containing samples in the highest viral load category (Ct values < 25) ranged between 44.7 and 91.1%, while they dropped to 8.7 to 22.7% for samples with intermediate Ct values (25)(26)(27)(28)(29)(30). In light of recent reports on the emergence of two novel Omicron-BA.2 subvariants, Omicron-BA.2.75 and BJ.1, awareness must be increased for the overall reduced detection rate and marked differences in RAT performance for these Omicron subvariants.…”

Vaccine-hesitant individuals accumulate additional COVID-19 risk due to divergent perception and behaviors related to SARS-CoV-2 testing – a population based, cross-sectional study

“…A disadvantage of RATs, however, is their low diagnostic and clinical sensitivity compared to PCR tests [11][12][13], and their enormous performance heterogeneity [14,15]. Particularly, the sensitivity to detect the nowadays predominant SARS-CoV-2 VoC omicron appears to be dismal using RATs [16][17][18], challenging the usefulness of RATs for COVID-19 diagnostics and surveillance, in particular in high-risk settings.…”