Implementing SARS-CoV-2 Rapid Antigen Testing in the Emergency Ward of a Swiss University Hospital: The INCREASE Study

Abstract

Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for patients' cohorting. RAT triaging in association with RT-PCR allowed us to promptly isolate positive patients and save resources. Among 532 patients, overall sensitivities were 48.3% for Exdia and 41.2% for Standard Q^®, Panbio^TM and BD Veritor™. All RATs exhibited specificity above 99%. Sensitivity increased to 74.6%, 66.2%, 66.2% and 64.8% for Exdia, Standard Q^®, Panbio^TM and BD Veritor™, respectively, for viral loads above 10⁵ copies/mL, to 100%, 97.8%, 96.6% and 95.6% for viral loads above 10⁶ copies/mL and 100% for viral loads above 10⁷ copies/mL. Sensitivity was significantly higher for patients with symptoms onset within four days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with the evolution of symptoms longer than four days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Among COVID-19 asymptomatic patients, sensitivity was 33%. All Immunoglobulin-A-positive patients resulted negative for RAT. The RAT might represent a useful resource in selected clinical settings as a complementary tool in RT-PCR for rapid patient triaging, but the lower sensitivity, especially in late presenters and COVID-19 asymptomatic subjects, must be taken into account.

Keywords: COVID-19 diagnostic testing; SARS-CoV-2; emergency ward; health plan implementation; nucleocapsid protein; rapid antigen test.

Figure 1

Diagnostic algorithm for managing tests flow according COVID-19 symptoms. Ag +: positive rapid antigen test. Ag −: negative rapid antigen test. RT-PCR: real-time polymerase chain reaction.

Figure 2

Antigen testing procedure with the reference test (Standard Q^®). (A) Fresh nasopharyngeal sample from a COVID-19 symptomatic patient received at the RAT laboratory. (B–C) A 350 µL volume of the sample is collected from the viral transport medium and (D) mixed with the extraction buffer, according to the manufacturer’s instructions. (E) Three drops of the extracted sample are applied to the testing device. (F) Results are readable in 15 to 30 min.

Figure 3

Number of patients included and time to results from patients’ registration to RAT or RT-PCR results. RAT: rapid antigen test. RT-PCR: reverse transcription-polymerase chain reaction. Pt: patients. H: hours. Please, note that the time-to-result analysis was performed on available results from 375 patients.

Figure 4

Comparison between four rapid antigen tests, showing the sensitivity according to the viral load. RAT: rapid antigen test. Viral load (VL) on the x-axis is expressed in logarithmic (log₁₀) scale. Please note that the Exdia test exhibited the best performances, with 75.9% sensitivity for VL > 10⁵ copies/mL and 100% sensitivity for VL > 10⁶ and 10⁷ copies/mL.

Figure 5

Cycle thresholds and viral loads of patients according to duration of symptoms and presence or absence of nasopharyngeal IgA.

Figure 6

Relationship between viral load, hypothetical contagiousness and correspondence with the sensitivity of (A) RAT and (B) RT-PCR (based on our evaluation).Viral load (VL) on the x-axis is expressed in a logarithmic (log₁₀) scale. The gray area represents a test sensitivity of <20%. The orange area represents a sensitivity of >20% but lower than 80%. The blue area represents a sensitivity of >80% but <95%. The green area represents a sensitivity above 95%. (A) The “Attention” symbol highlights the orange dashed critical zone where SARS-CoV-2 is already contagious but the sensitivity of the RAT is not acceptable, being very low (30–60%) for VL between 10⁴ and 10⁵ and low (60–80%) for VL between 10⁵ and 10⁶.Contagiousness is estimated to be negligible when R0 < 0.01, very low when R0 > 0.01 and <0.05, significant when R0 > 0.05 and < 0.2 and high when R0 > 0.2 over a 24 h period in the same room than another patient.