Performance of SARS-CoV-2 Antigen-Detecting Rapid Diagnostic Tests for Omicron and Other Variants of Concern

Abstract

The SARS-CoV-2 antigen-detecting rapid diagnostic test (Ag-RDTs) is an easy-to-use diagnostic tool to identify the contagious individuals and reduce the new infections. However, to be effective, Ag-RDTs require the detection of distinct variants of concern (VOC) with high analytical sensitivity. Here, we found that the VOC diverge at the nucleocapsid protein used by four commercial Ag-RDTs for the viral detection. Relative to the original D614G variant, there was a 10-fold loss of detection for the Delta and Alpha variants in certain Ag-RDTs, a reduction above the threshold required to isolate the viable virus. However, Beta and Omicron variants did not lose the detection capacity. As the new VOC arise, successful contact tracing requires continuous monitoring of Ag-RDTs performance.

Keywords: SARS-CoV-2; antigen-detecting rapid diagnostic tests; diagnosis; nucleocapsid (N); variants of concern.

FIGURE 1

Nucleocapsid mismatches and quantification of the SARS-CoV-2 variants. (A) Nucleotide mismatches or deletions (represented by the colored lines of the legend) and amino acid changes indicated by codon position sequenced in the nucleocapsid of distinct SARS-CoV-2 variants as compared to the original Wuhan virus (as reference). (B) Nucleocapsid concentration measured by qPCR (log₁₀ of viral N2 RNA copies/ml) and ELISA (ng of nucleocapsid/ml) for all variants analyzed at the first dilution tested in the Ag-RDTs.

FIGURE 2

Comparative detection of SARS-CoV-2 variants by four commercial Ag-RDTs and correlation with nucleocapsid copies per ml. (A) Detection of 4 VOC using a 1:19 ratio of sample-to-buffer volume (10 μl:190 μl). (B) Detection of six variants using a 1:1 ratio of sample-to-buffer volume (100 μl:100 μl). The results for 1/10 viral dilutions tested in duplicate are indicated for each variant and commercial Ag-RDTs. Red boxes indicate variant-Ag-RDTs combination with reduced detection capacity as compared to D614G. (C) The detection range shown as values of the viral N2 RNA (in log₁₀ of copies/ml). The range above the first 10-fold dilution with positive results of detection is shown in green, while the range below the first 10-fold dilution with negative results is depicted in red for each Ag-RDTs and every variant at the ratio 1:1.