SARS-CoV-2 antigen tests for screening of healthcare workers; experience with over 48,000 combined antigen tests and RT-PCR tests

Abstract

Background: To prevent spread to patients and co-workers, health care workers (HCWs) infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) should quickly be identified. Although real time polymerase chain reaction (RT-PCR) is the gold standard, this test takes several hours, during which a HCW is unable to work. Antigen (Ag) tests may be an efficacious means of screening HCWs since they are easy to perform and provide fast results.

Methods: In this study, 48,010 paired results of Ag-testing and RT-PCR, performed on HCWs between January 2021 and April 2022, were evaluated to determine the diagnostic accuracy of SARS-CoV-2 Ag-tests in diagnosing potentially infectious individuals. This analysis was performed with cycling threshold values (Ct-values) ≤30 and ≤25 as cut-offs.

Results: Respectively 3.1% (n = 1507) and 0.3% (n = 140) of Ag-tests were positive or indeterminate, and thus indicative for SARS-CoV-2 infection. In total, 2479 (5.2%) RT-PCRs were positive, of which 1529 (61.7%) had a Ct-value ≤25 and 402 (16.2%) a Ct-value between 26 and 30. At Ct-value ≤30 as a cut-off, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Ag-tests were 79.0%, 99.8%, 93.8% and 99.1%, respectively. At Ct-value ≤25, sensitivity further improved to 92.0%, by which the NPV increased to 99.7%.

Conclusions: To prevent transmission from HCWs to patients and co-workers, while maintaining workforce capacity, Ag-tests are a valuable addition to RT-PCR tests, as they have a quick turnaround time and excellent sensitivity for identifying individuals with high potential for transmission.

Keywords: Antigen test; Health care worker; Hospital management; Infection prevention; Real-time polymerase chain reaction; SARS-CoV-2.

Fig. 1

Schematic overview of health care worker testing regime. Health care worker (HCW) screening was divided into five different phases. Phase 1 (T = 0 min) was generally performed by the health care worker himself/herself. Indication for testing was based on (1) signs and/or symptoms of a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 infection), (2) close contact with a known positive person, or (3) after travelling to endemic areas as defined by the European Center of Disease Prevention and Control (ECDC) [2,5,6]. In phase 2 (T = 0 min), the test regime was determined. Asymptomatic or mild-symptomatic individuals planning to go to work in the University Medical Center Groningen (UMCG) (instead of at home) on the day of testing were tested with both a SARS-CoV-2 antigen (Ag) test and a SARS-CoV-2 Real-time polymerase chain reaction (RT-PCR). Otherwise, only SARS-CoV-2 RT-PCR was performed. In phase 3 (T = 15–30 min), based on the Ag-test result, it was decided whether a HCW was allowed to work at location awaiting the RT-PCR result (i.e. when the Ag-test result was negative), or should await the PCR result at home (when the Ag-test result was indeterminate (IND) or positive). In phase 4 (T ≤ 8 h), based on the RT-PCR result, the final decision was made on whether a HCW was allowed to work at location or should go into isolation.

Fig. 2

Number of screenings per health care worker, Ag-test types and test results. (A) The number of tests for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection performed per individual health care worker (HCW) for the population tested with the combination of an antigen (Ag) test and Real-time polymerase chain reaction (RT-PCR) (n = 48,010 tests, n = 10,381 HCWs). Bars represent the total number of HCWs, colors represent the total number of screenings per individual HCW (ranging from 1 screening to over 31 screenings per HCW). (B) Types of Ag-tests used to screen HCWs for SARS-CoV-2 during the dominancy of Alpha, Delta and Omicron SARS-CoV-2 variants. Included population is the population screened with both RT-PCR and Ag-test (n = 48,010 tests). (C-D) Test results of (C) Ag-tests and (D) RT-PCR tests. The total circle represents all tests (n = 48,010), and different sections of the circle the part of total. See Supplemental Table 2 for exact numbers per section.

Fig. 3

Association of Ag-test diagnostic accuracy with RT-PCR Ct-values. (A) Distribution of Cycling threshold values (Ct-values) as acquired by real time polymerase chain reaction (RT-PCR) for false negative antigen (Ag) test results (black bars) and true positive Ag-test results (pink bars). RT-PCR results were taken as the reference standard for the Ag-tests. Bin Center=1. Bars represent absolute numbers. (B) Sensitivity (red dots) and specificity (green squares) of the Ag-tests at different Ct-value cut-offs as reference standard. Sensitivity and specificity are represented as percentages.