key: cord-0840444-z2blr7l6
authors: Wachinger, Jonas; Olaru, Ioana Diana; Horner, Susanne; Schnitzler, Paul; Heeg, Klaus; Denkinger, Claudia M.
title: The potential of SARS-CoV-2 antigen-detection tests in the screening of asymptomatic persons
date: 2021-07-26
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.07.020
sha: ef958724c2eb5a94f86bbb9ee0487f33a74506c9
doc_id: 840444
cord_uid: z2blr7l6

OBJECTIVES: To assess the performance of antigen-based rapid diagnostic tests (Ag-RDTs) for SARS CoV-2 when implemented for large-scale universal screening of asymptomatic individuals. METHODS: This study is a pragmatic implementation study for universal Ag-RDT-based screening at a tertiary care hospital in Germany where patients presenting for elective procedures and selected personnel without symptoms suggestive of SARS-CoV-2 were screened with an Ag-RDT since October 2020. Test performance was calculated on an individual-patient level. RESULTS: In total, 49,542 RDTs were performed in 27,199 asymptomatic individuals over a duration of five months. Out of 222 positive results, 196 underwent in-house confirmatory testing with PCR, out of which 170 were confirmed positive, indicating a positive predictive value (PPV) of 86.7% (95%CI 81.2-91.1%). Negative Ag-RDTs were not routinely tested with PCR, but a total of 94 cases of false negative Ag-RDTs were detected due to PCR tests being performed within the following five days with a median CT-value of 33 (IQR 29-35). CONCLUSIONS: This study provides evidence that Ag-RDTs can have a high diagnostic yield for transmission relevant infections with limited false-positives when utilized at the point of care on asymptomatic patients and thus can be a suitable public-health test for universal screening.

Several researchers and policy makers, supported by evidence from modelling studies, have 43 recently argued to increase large-scale screening for SARS-CoV-2 to curb transmission from 44 patients with minimal or no symptoms [1] [2] [3] [4] [5] . Antigen-detection point-of-care rapid diagnostic 45 tests (Ag-RDTs) have shown very good sensitivity (88%) in persons with high viral load (CT 46 <30) along with high specificity (>99%) [6, 7] . With their favourable ease-of-use, rapid turn-47 around, and good (although suboptimal) performance, Ag-RDTs meet the characteristics for a 48 test for public health use and could allow for better control of transmission if implemented in 49 well-designed universal screening strategies [8, 9] . However, one frequently raised concern has 50 been the potentially imperfect specificity, leading to large numbers of false-positives when 51

using Ag-RDTs in large-scale screening strategies with low prevalence [10] , which could 52 conceivably disrupt workflows and undermine trust in the test. Furthermore, in a setting where 53 high-risk persons are present (e.g., hospital), concerns exist regarding imperfect sensitivity 54 leading to secondary cases and substantial morbidity and mortality. Data from large scale 55 screening implementation efforts that would allow to gauge diagnostic yield and issues with 56 false-positives are limited. 57 58

We performed a large-scale, pragmatic implementation study of Ag-RDTs in the context of a 60 universal screening program at one of Germany's largest tertiary care hospitals (Heidelberg 61 University Hospital, Germany) serving over 100,000 inpatients and 1.3 million outpatients per 62

year [11] . The study was conducted between 20 September 2020 and 7 March 2021 during 63

Germany's second wave of COVID-19. Over the duration of the study, SARS-CoV-2 incidence 64 in the region served by the hospital ranged from 11.6 cases per 100,000 inhabitants in the last 65 To the best of our knowledge, this is the first large-scale implementation study of a universal 138 screening program of asymptomatic individuals to analyse the diagnostic yield of SARS-CoV-139 symptomatic patients. Additionally, the delay in confirmatory PCR-based testing merits 143 caution when interpreting the sensitivity and specificity estimates. 144

In conclusion, this study provides evidence that an Ag-RDT can be a suitable test for large-145 scale universal screening in a hospital setting and adds the important component of a public-146 health test to our diagnostic armamentarium. Even as vaccination rates continue to increase, 147

given the emergence of novel virus variants, resulting immune escape despite vaccination, and 148 the high risk associated with undetected infections in clinical settings, we expect universal 149 screening to remain necessary as the pandemic progresses. 150 JW, KH, and CMD conceptualized the study. IDO analysed the data, supported by JW, SH, 169 PS, and CMD. JW, IDO, and CMD drafted the manuscript. All co-authors critically revised 170 and approved the final version of the research note. 171

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Mr Wachinger, Dr. Olaru, Mrs Horner, Dr. Schnitzler, and Dr. Heeg have nothing to disclose; 153Dr. Denkinger reports grants from Ministry of Science, Research and Culture, State of Baden 154Wuerttemberg, Germany, during the conduct of the study. The authors did not receive any 155 industry support for conducting this study. Within the previous three years, CMD has received 156 support from Systemanalyse Programmentwicklung (SAP), and PS has received support from