Importance of external quality assessment for SARS-CoV-2 antigen detection during the COVID-19 pandemic

Abstract

Background: Antigen testing has become an essential part of fighting the ongoing COVID-19 pandemic. With the continual increase in available tests, independent and extensive comparative evaluations using data from external quality assessment (EQA) studies to evaluate test performance between different users are required.

Objectives: An EQA scheme was established to assess the sensitivity of antigen tests and the potential impact of circulating SARS-CoV-2 strains on their performance.

Study design: Panels were prepared for three challenges in 2021 containing inactivated SARS-CoV-2-positive samples of various genetic strains (including variants of concern, VOCs) at different concentrations, and negative samples. Data was analysed based on qualitative testing results in relation to the antigen test used.

Results: Participants registered for each individual challenge in any combination. In total, 258 respondents from 27 countries worldwide were counted submitting 472 datasets. All core samples were correctly reported by 76.7 to 83.1% at participant level and by 73.5 to 83.8% at dataset level. Sensitivity differences could be shown in viral loads and SARS-CoV-2 strains/variants including the impact on performance by a B.1.1.7-like mutant strain with a deletion in the nucleoprotein gene. Lateral flow rapid antigen tests showed a higher rate of false negatives in general compared with automated point-of-care tests and laboratory ELISA/immunoassays.

Conclusions: EQA schemes can provide valuable data to inform participants about weaknesses in their testing process or methods and support ongoing assay evaluations for regulatory approval or post-market surveillance.

Keywords: Antigen test; COVID-19 testing; Quality assurance; SARS-CoV-2 variants; Sensitivity; Severe acute respiratory syndrome.

Fig. 1

Participants per country. The chart shows the total number of participants per country in the three open challenges of the first QCMD 2021 SARS-CoV-2 Antigen Testing EQA Study. Each participant was only counted once, independently of the frequency of participation. The absolute number of participants and the percentage followed by their frequency of participation as respondents per country are displayed (n,% I No. of respondents).

Fig. 2

Reported type of organisation. The chart shows the absolute numbers for different organisation types, where antigen testing has been conducted, as reported by the participants in a survey during the results submission. Please note, three of the 197 participants reported data for two different testing sites, i.e., laboratory and mobile testing unit.