Can the Rapid Antigen Test for COVID-19 Replace RT-PCR: A Meta-analysis of Test Agreement

Elmakaty, I. M.; Elsayed, A. A.; Hommos, R. G.; Abdo, R. S.; Mohamed, A. G.; Yousif, Z. B.; Fakhroo, M. M.; Alansari, A. A.; Coyle, P. V.; Doi, S. A. R.

Background Several studies have compared the performance of reverse transcription-polymerase chain reaction (RT-PCR) and antigen rapid diagnostic tests (Ag-RDTs) as tools to diagnose SARS-CoV-2 disease (COVID-19). As the performance of Ag-RDT may vary among different products and viral load scenarios, the clinical utility of the Ag-RDT remains unclear. Our aim is to assess the diagnostic agreement between Ag-RDTs and RT-PCR in testing for COVID-19 across different products and cycle threshold (Ct) values. Methods An evidence synthesis and meta-analysis of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) was conducted after an exhaustive search of five databases to locate published studies that compared Ag-RDT to RT-PCR and reported quantitative comparison results. After the screening, quality assessment, and data extraction, the synthesis of pooled estimates was carried out utilizing the quality-effects (QE) model and Freeman-Tukey double arcsine transformation (FTT) for variance stabilization. Subgroup analysis was also conducted to evaluate the tests diagnostic agreement across distinctive products and Ct-value thresholds. Findings A total of 420 studies were screened by title and abstract, of which 39 were eventually included in the analysis. The overall NPA was 99.4% (95%CI 98.8-99.8, I2=91.40%). The PPA was higher in lower Ct groups such as groups with Ct <20 and Ct <25, which had an overall PPA of 95.9% (95%CI 92.7-98.2, I2=0%) and 96.8% (95%CI 95.2-98.0, I2=50.1%) respectively. This is in contrast to groups with higher Ct values, which had relatively lower PPA. Panbio and Roche Ag-RDTs had the best consistent overall PPA across different Ct groups especially in groups with Ct <20 and Ct <25. Interpretation The findings of our meta-analysis support the use of Ag-RDTs in lieu of RT-PCR for decision making regarding COVID-19 control measures, since the enhanced capacity of RT-PCR to detect disease in those that are Ag-RDT negative will be unlikely to have much public health utility. This step will drastically reduce the cost and time in testing for COVID-19.