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

Abstract

The emergence of each novel SARS-CoV-2 variant of concern (VOC) requires investigation of its potential impact on the performance of diagnostic tests in use, including antigen-detecting rapid diagnostic tests (Ag-RDTs). Although anecdotal reports have been circulating that the newly emerged Omicron-BA.1 variant is in principle detectable by Ag-RDTs, few data on sensitivity are available. We have performed (i) analytical sensitivity testing with cultured virus in eight Ag-RDTs and (ii) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron-BA.1 (n = 59) or Delta (n = 54) breakthrough infection on seven Ag-RDTs. Overall, in our analytical study we have found heterogenicity between Ag-RDTs for detecting Omicron-BA.1. When using cultured virus, we observed a trend toward lower endpoint sensitivity for Omicron-BA.1 detection than for earlier circulating SARS-CoV-2 and the other VOCs. In our retrospective study, the detection of Delta and Omicron-BA.1 was assessed in a comparable set of stored clinical samples using seven Ag-RDTs. Four hundred ninety-seven of all 826 tests (60.17%) performed on Omicron-BA.1 samples were positive, compared to 489/756 (64.68%) for Delta samples. In the analytical study, the sensitivity for both Omicron-BA.1 and Delta between the Ag-RDTs was variable. All seven Ag-RDTs showed comparable sensitivities to detect Omicron-BA.1 and Delta in the retrospective study. IMPORTANCE 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.

Keywords: COVID-19; Omicron variant; Omicron-BA.1 variant; SARS-CoV-2; antigen-detecting rapid diagnostic tests; variants of concern.

FIG 1

Heatmap based on log₁₀ PFU per milliliter (A) and on RNA viral load ranges (B) for analytical sensitivity of eight Ag-RDTs with an early-pandemic SARS-CoV-2 isolate (B.1.610) and the VOCs Alpha, Beta, Gamma, and Delta in comparison to Omicron-BA.1. Note that analytical sensitivities for early-pandemic SARS-CoV-2 B.1.610, Alpha, Beta, Gamma, and Delta have already been published before but were added here for consistency reasons and better interpretability of the data on Omicron-BA.1 (15, 30).

FIG 2

Heatmap of retrospective testing of original nasopharyngeal patient swab specimens from Omicron-BA.1 (n = 59) and Delta (n = 54) breakthrough infections in seven Ag-RDTs per SARS-CoV-2 log₁₀ RNA copies per milliliter, performed in duplicates. Infectious virus was detected from all patient specimens unless marked with an asterisk (*, no infectious virus isolated).

FIG 3

Percentage of positive/negative results for Omicron-BA.1 and Delta vaccine breakthrough infections per number of tests performed (Omicron-BA.1, n = 118; Delta, n = 108). ns, nonsignificant.