OBJECTIVE: This paper motivates and justifies the use of antigen tests for epidemic control as distinct from a diagnostic test. STUDY DESIGN AND SETTING: We discuss the relative advantages of antigen and PCR tests, summarizing evidence from both the literature as well as Austrian schools, which conducted frequent, mass rapid antigen testing during the spring of 2021. While our report on testing predates Delta, we have updated the review with recent data on viral loads in breakthrough infections and more information about testing efficacy, especially in children. RESULTS: Rapid antigen tests detect proteins at the surface of virus particles, identifying the disease during its infectious phase. In contrast, PCR tests detect viral genomes: they can thus diagnose COVID-19 before the infectious phase but also react to remnants of the virus genome, even weeks after live virus ceases to be detectable in the respiratory tract. Furthermore, the logistics for administering the tests are different. Large-scale rapid antigen testing in Austrian schools showed low false-positive rates along with an approximately 10% lower effective reproduction number in the tested cohort. CONCLUSION: Using antigen tests at least 2-3 times per week could become a powerful tool to suppress the COVID-19 pandemic.

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Epidemiology Center for Public Health Medical University of Vienna Austria

Division of Biosciences University College London London UK

Faculty of Mathematics University of Vienna Austria

Institute of Statistics and Mathematical Methods in Economics TU Wien Austria

Zobrazit více v PubMed

UK COVID-19 Lateral Flow Oversight Team COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing. Infect Dis (except HIV/AIDS) 2021 doi: 10.1101/2021.01.13.21249563. PubMed DOI

Kissler SM, Fauver JR, Mack C, Olesen SW, Tai C, Shiue KY, et al. Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies. PLOS Biol. 2021;19 doi: 10.1371/journal.pbio.3001333. PubMed DOI PMC

Mina MJ, Parker R, Larremore DB. Rethinking Covid-19 test sensitivity — a strategy for containment. N Engl J Med. 2020;383:e120. doi: 10.1056/NEJMp2025631. PubMed DOI

Crozier A, Rajan S, Buchan I, McKee M. Put to the test: use of rapid testing technologies for covid-19. BMJ. 2021;372 doi: 10.1136/bmj.n208. PubMed DOI

Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure. Ann Intern Med. 2020;173:262–267. doi: 10.7326/M20-1495. PubMed DOI PMC

Smith RL, Gibson LL, Martinez PP, Ke R, Mirza A, Conte M, et al. Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. MedRxiv. 2021 doi: 10.1101/2021.03.19.21253964. PubMed DOI PMC

Larremore DB, Wilder B, Lester E, Shehata S, Burke JM, Hay JA, et al. Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening. Sci Adv. 2021;7:eabd5393. doi: 10.1126/sciadv.abd5393. PubMed DOI PMC

Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J, Ho A. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Lancet Microbe. 2021;2:e13–e22. doi: 10.1016/S2666-5247(20)30172-5. PubMed DOI PMC

Kissler SM, Fauver JR, Mack C, Tai CG, Breban MI, Watkins AE, et al. Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated persons. N Engl J Med. 2021;0 doi: 10.1056/NEJMc2102507. null. PubMed DOI PMC

Cevik M, Kuppalli K, Kindrachuk J, Peiris M. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. 2020:m3862. doi: 10.1136/bmj.m3862. PubMed DOI

Chia PY, Ong SWX, Chiew CJ, Ang LW, Chavatte J-M, Mak T-M, et al. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study. Clin Microbiol Infect. 2021;0 doi: 10.1016/j.cmi.2021.11.010. PubMed DOI PMC

Glenet M, Lebreil A-L, Heng L, N'Guyen Y, Meyer I, Andreoletti L. Asymptomatic COVID-19 adult outpatients identified as significant viable SARS-CoV-2 shedders. Sci Rep. 2021;11:20615. doi: 10.1038/s41598-021-00142-8. PubMed DOI PMC

Chau NVV, Ngoc NM, Nguyet LA, Quang VM, Ny NTH, Khoa DB, et al. An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam. EClinicalMedicine. 2021;41 doi: 10.1016/j.eclinm.2021.101143. PubMed DOI PMC

Lee LY, Rozmanowski S, Pang M, Charlett A, Anderson C, Hughes GJ, et al. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infectivity by viral load, S gene variants and demographicfactors, and the utility of lateral flow devices to prevent transmission. Clin Infect Dis. 2021;ciab421 doi: 10.1093/cid/ciab421. PubMed DOI PMC

Marks M, Millat-Martinez P, Ouchi D, Roberts C h, Alemany A, Corbacho-Monné M, et al. Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study. Lancet Infect Dis 2021:S1473309920309853. https://doi.org/10.1016/S1473-3099(20)30985-3. PubMed PMC

Shamier MC, Tostmann A, Bogers S, Wilde J de, IJpelaar J, Kleij WA van der, et al. Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers. 2021. https://doi.org/10.1101/2021.08.20.21262158.

Smith RL, Gibson LL, Martinez PP, Ke R, Mirza A, Conte M, et al. Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. J Infect Dis 2021. https://doi.org/10.1093/infdis/jiab337. PubMed PMC

Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. 2020;323:2249–2251. doi: 10.1001/jama.2020.8259. PubMed DOI

Korevaar DA, Toubiana J, Chalumeau M, McInnes MDF, Cohen JF. Evaluating tests for diagnosing COVID-19 in the absence of a reliable reference standard: pitfalls and potential solutions. J Clin Epidemiol. 2021;138:182–188. doi: 10.1016/j.jclinepi.2021.07.021. PubMed DOI PMC

UK Health Security Agency. Testing at private lab suspended following NHS Test and Trace investigation. GOVUK n.d. https://www.gov.uk/government/news/testing-at-private-lab-suspended-following-nhs-test-and-trace-investigation (accessed December, 2021).

Liu Y, Eggo RM, Kucharski AJ. Secondary attack rate and superspreading events for SARS-CoV-2. Lancet. 2020;395:e47. doi: 10.1016/S0140-6736(20)30462-1. PubMed DOI PMC

Adam DC, Wu P, Wong JY, Lau EHY, Tsang TK, Cauchemez S, et al. Clustering and superspreading potential of SARS-CoV-2 infections in Hong Kong. Nat Med. 2020;26:1714–1719. doi: 10.1038/s41591-020-1092-0. PubMed DOI

Johnson KD, Beiglböck M, Eder M, Grass A, Hermisson J, Pammer G, et al. Disease momentum: Estimating the reproduction number in the presence of superspreading. Infect Dis Model. 2021;6:706–728. doi: 10.1016/j.idm.2021.03.006. PubMed DOI PMC

Lindner AK, Nikolai O, Kausch F, Wintel M, Hommes F, Gertler M, et al. Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with self-collected anterior nasal swab versus professional-collected nasopharyngeal swab. Infect Dis (except HIV/AIDS) 2020 doi: 10.1101/2020.10.26.20219600. PubMed DOI PMC

Epimath: SEIR team. SEIR Simulator 2021. https://epimath.at/en/seir/ (accessed February, 2021).

ORF. Stichprobenstudie: CoV-Dunkelziffer deutlich gestiegen. newsORF.at 2020. https://orf.at/stories/3191333 /(accessed February, 2021).

der Standard, riss. Nasenbohrertest an Schulen: 470.000 Tests brachten 198 positive Fälle 2021. https://www.derstandard.de/story/2000124065253/nasenborertest-an-schulen-fassmann-faengt-200-dicke-fische (accessed February, 2021).

APA. Die­se Woche rund 900 posi­ti­ve Selbst­tests an Schulen 2021. https://science.apa.at/power-search/8002604952673151401 (accessed March, 2021).

APA. Die­se Woche 1.200 posi­ti­ve Coro­na-Schnell­tests an Schulen 2021. https://science.apa.at/power-search/2029377885706078301 (accessed March, 2021).

APA. Erneut rund 1.200 posi­ti­ve Selbst­tests an Schulen 2021. https://science.apa.at/power-search/11936563920681969712 (accessed March, 2021).

APA . 2021. Die­se Woche 1.325 posi­ti­ve Coro­na-Selbst­tests an Schulen. https://science.apa.at/power-search/14147055413057601800 (accessed March 23, 2021)

APA . 2021. 1.400 posi­ti­ve Coro­na-Selbst­tests an Schulen. https://science.apa.at/power-search/14565446232237996566 (accessed March 29, 2021)

Pollán M., Pérez-Gómez B., Pastor-Barriuso R., Oteo J., Hernán M.A., Pérez-Olmeda M., et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. The Lancet. 2020;396:535–544. doi: 10.1016/S0140-6736(20)31483-5. PubMed DOI PMC

Tönshoff B., Müller B., Elling R., Renk H., Meissner P., Hengel H., et al. Prevalence of SARS-CoV-2 infection in children and their parents in southwest Germany. JAMA Pediatr. 2021 doi: 10.1001/jamapediatrics.2021.0001. PubMed DOI PMC

Pollock N.R., Jacobs J.R., Tran K., Cranston A.E., Smith S., O'Kane C.Y., et al. Performance and implementation evaluation of the Abbott BinaxNOW rapid antigen test in a high-throughput drive-through community testing site in Massachusetts. J Clin Microbiol. 2021;59 doi: 10.1128/JCM.00083-21. e00083-21https://doi.org/ PubMed DOI PMC

Epimath: R-Nowcasting team . 2021. R-Nowcasting. https://epimath.at/now/ (accessed March 23, 2021)

Mina M., Miller S., Quigley M., Prentiss T., McKinnon J.E., Comer S. 2020. Analyzing conflicting results in rapid point-of-care COVID-19 testing.

Willeit P., Krause R., Lamprecht B., Berghold A., Hanson B., Stelzl E., et al. Prevalence of RT-PCR-detected SARS-CoV-2 infection at schools: First results from the Austrian School-SARS-CoV-2 Study. MedRxiv. 2021 doi: 10.1101/2021.01.05.20248952. 2021.01.05.20248952. https://doi.org/ PubMed DOI PMC

Young B.C., Eyre D.W., Kendrick S., White C., Smith S., Beveridge G., et al. A cluster randomised trial of the impact of a policy of daily testing for contacts of COVID-19 cases on attendance and COVID-19 transmission in English secondary schools and colleges. Infectious Diseases (except HIV/AIDS) 2021 doi: 10.1101/2021.07.23.21260992. PubMed DOI PMC

Brauner J.M., Mindermann S., Sharma M., Johnston D., Salvatier J., Gavenčiak T., et al. Inferring the effectiveness of government interventions against COVID-19. Science. 2021;371 doi: 10.1126/science.abd9338. PubMed DOI PMC

Mendez-Brito A., El Bcheraoui C., Pozo-Martin F. Systematic review of empirical studies comparing the effectiveness of non-pharmaceutical interventions against COVID-19. J Infect. 2021 doi: 10.1016/j.jinf.2021.06.018. PubMed DOI PMC

Dinnes J., Deeks J.J., Adriano A., Berhane S., Davenport C., Dittrich S., et al. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev. 2020 doi: 10.1002/14651858.CD013705. PubMed DOI PMC

Mina M.J., Peto T.E., García-Fiñana M., Semple M.G., Buchan I.E. Clarifying the evidence on SARS-CoV-2 antigen rapid tests in public health responses to COVID-19. The Lancet 2021. https://doi.org/ 10.1016/S0140-6736(21)00425-6. PubMed PMC

Mina M.J., Andersen K.G. COVID-19 testing: One size does not fit all. Science. 2021;371:126–127. doi: 10.1126/science.abe9187. PubMed DOI

Scheiblauer H., Filomena A., Nitsche A., Puyskens A., Corman V.M., Drosten C., et al. Comparative sensitivity evaluation for 122 CE-marked rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021. Eurosurveillance. 2021;26 doi: 10.2807/1560-7917.ES.2021.26.44.2100441. PubMed DOI PMC

Adams S.H., Schaub J.P., Nagata J.M., Park M.J., Brindis C.D., Irwin C.E. Young Adult Perspectives on COVID-19 Vaccinations. J Adolesc Health. 2021;0 doi: 10.1016/j.jadohealth.2021.06.003. PubMed DOI PMC

Mishra A., Sutermaster S., Smittenaar P., Stewart N., Sgaier S.K. COVID-19 Vaccine Coverage Index: Identifying barriers to COVID-19 vaccine uptake across U.S. counties. MedRxiv. 2021 doi: 10.1101/2021.06.17.21259116. 2021.06.17.21259116. https://doi.org/ DOI

Rane M.S., Kochhar S., Poehlin E., You W., Robertson M., Zimba R., et al. Determinants of COVID-19 vaccine hesitancy and vaccine uptake in a national cohort of U.S. adults. MedRxiv. 2021 doi: 10.1101/2021.05.12.21257116. PubMed DOI PMC

Ward H., Whitaker M., Tang S.N., Atchison C., Darzi A., Donnelly C.A., et al. Vaccine uptake and SARS-CoV-2 antibody prevalence among 207,337 adults during May 2021 in England: REACT-2 study. MedRxiv. 2021 doi: 10.1101/2021.07.14.21260497. DOI

Cohn B.A., Cirillo P.M., Murphy C.C., Krigbaum N.Y., Wallace A.W. SARS-CoV-2 vaccine protection and deaths among US veterans during 2021. Science. 2022;0:eabm0620. doi: 10.1126/science.abm0620. PubMed DOI PMC

Eyre D.W., Taylor D., Purver M., Chapman D., Fowler T., Pouwels K.B., et al. 2021. The impact of SARS-CoV-2 vaccination on Alpha & Delta variant transmission. PubMed DOI