In the current research, we studied the sensitivity and specificity of Ag-RDT in asymptomatic COVID-19 cases in a field-based scenario during the Shanghai COVID-19 quarantine period. We found that the Ag-RDT showed a satisfied specificity (100%). Although the sensitivity was relatively low for the entire samples (43.37%), the Ag-RDT demonstrated a good sensitivity for the subset of individuals with an RT-PCR Ct value of the N gene in the < 20 range (84.21%). This result indicated that Ag-RDT could be a reliable alternative to RT-PCR for the rapid detection of the individual with a higher risk of infectivity in mass screening of asymptomatic populations.
Diagnostic testing for SARS-CoV-2 is a critical constituent of the COVID-19 prevention and control strategy. According to the WHO interim guidance, the RT-PCR has the best sensitivity and specificity and is recommended as the reference standard for SARS-CoV-2 diagnosis . However, the RT-PCR is a time-consuming process and required specialized laboratory infrastructures and capacity. Thus, in the last two years, commercialized Ag-RDTs were introduced to the market, aiming to offer an opportunity to increase the availability and speed of testing in appropriate scenarios. According to WHO, eligible Ag-RDT for SARS-COV-2 needs to meet the minimum performance requirements of ≥ 80% sensitivity and ≥ 97% specificity . Similarly, the European Center for Disease Prevention and Control also suggests the use of Ag-RDT with performance closer to RT-PCR, i.e., ≥ 90% sensitivity and ≥ 97% specificity . However, while the overall specificity met the WHO suggested standard (99.6%, 95% CI 99.0–99.8%) , several commercialized Ag-RDTs demonstrated a lack of sensitivity. According to a recent Cochrane study enrolling eight studies, the average sensitivity of the commercialized Ag-RDT corresponds to only 56.2% (95% CI 29.5–79.8%) for the general population . Specifically, for symptomatic SARS-COV-2-infected individuals, the average sensitivity was 72.0% (95% CI 63.7–79.0%) , which was higher than that of the asymptomatic individuals (58.1%, 95% CI 40.2–74.1%). Baro et al.  conducted a head-to-head comparison of five Ag-RDTs for SARS-CoV-2 asymptomatic infection. They found that all these Ag-RDTs acquired high specificity (all > 89%). However, the overall sensitivity of Abbott, Siemens, Roche, and Lepu kits were only 38.61%, 51.49%, 43.56%, 45.54%, and 28.71%, respectively. Among those who had lower Ct values (< 30), the corresponding sensitivity increased to 66.67%, 86.67%, 83.33%, 83.33%, and 70%, respectively, which, however, remained below the minimum performance requirements of WHO and European Center for Disease Prevention and Control. Within our panel of clinical samples, the Ag-RDT used in the current study was proved to be highly specific and the sensitivity parament was overall in line with the previous report.
Our study has several limitations. First, it is expected that the types of SARS-CoV-2 variants are emerging. Previous studies had already demonstrated the variable performance of Ag-RDTs against different SARS-CoV-2 variants [19, 20]. Since SARS-CoV-2 culture and sequencing were not performed in the current study, the exact sensitivity of the current Ag-RDTs remained inconclusive for different SARS-CoV-2 variants. According to the literature, the Omicron was the major viral strain during the study period [21, 22]. Thus, we believe that the results of the current study mainly reflected the performance of Ag-RDT targeting the Omicron. Secondly, this field evaluation was performed from April to May. Although Shanghai had a low circulation of other frequent respiratory viruses, this issue had not been fully excluded, which could affect the specificity of Ag-RDTs. Thirdly, it is worth mentioning that all the respiratory samples enrolled in the current study were collected by trained nurses. Since operating personnel has been previously suggested to affect the testing performance of Ag-RDT significantly , we expected to achieve a lower sensitivity of the Ag-RDT during the screening of the general population. Additionally, the moderate sample size is another limitation for accurately evaluating the test performance of Ag-RDT.