Conclusions
TB, low infection, HTN, infection, TJA
INFECTION, HTN
The pandemic developed in a highly dynamic manner in most countries, with scarcely comparable trends. The succession of gradually increasing bouts of infection has been interrupted by periods of low infection activity. There is no reason to believe that future pandemics with similar hazard potential will evolve in a less chaotic manner; therefore, SARS-CoV-2 can be seen as a blueprint for future outbreaks. Therefore, rapidly deployable outbreak surveillance systems should be developed and put on standby.Continuous active SARS-CoV-2 surveillance based on general population representative random samples of individuals or households and postal mailing of gargle sample collection kits for low-barrier home-based self-sampling, combined with a rapid, highly sensitive, and specific nucleic acid amplification test, is a feasible way to detect presymptomatic and asymptomatic cases without overburdening PCR capacities. However, additional measures are required to improve participation. Information material and consent processes should be tailored to real-life routine rather than scientific trials. In addition, the information material should be more concise and tested in pilot studies.The authors would like to thank the local health authority Rhine-Neckar for their valuable support and the successful collaboration, with special thanks to Dr Britta Knorr, Dr Rainer Schwertz, Dr Andreas Welker, and Doreen Kuss. The authors would also like to thank Daniel Ürge and Victoria Witte for their contribution to the reverse transcription loop-mediated isothermal amplification analysis. Claudiu Grozea from the European Molecular Biology Laboratory produced the gargling and sampling demonstration video for the study website. In addition, the authors would like to thank the cohort of students who supported this study with the assembly and shipment of sample collection kits as well as sample processing, their service in the hotline, and support in data processing and analyses. Nicholas Kyei and Miriam Compton kindly proofread the manuscript. Finally, the authors would like to thank all the individuals and households of the Rhine-Neckar region in the state Baden-Württemberg in Germany who responded to their request and provided the survey data and gargle samples. The Cov Surv study was embedded in the nationwide research network “Applied Surveillance and Testing” (Bundesweites Forschungsnetz “Angewandte Surveillance und Testung,” B-FAST) and the University Medicine’s Network (Netzwerk Universitätsmedizin, NUM) for COVID-19 research in Germany. The trial was financed by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF). The laboratory robot was funded within the framework of the Excellence Strategy of the Federal and State Governments of Germany and by the Ministry of Science, Research and the Arts Baden-Württemberg. For the publication fee we acknowledge financial support by Deutsche Forschungsgemeinschaft (DFG) within the funding program “Open Access Publikationskosten” as well as by Heidelberg University. The funders had no role in the study design, data collection, data analysis, interpretation of data, or writing of the manuscript.Authors' Contributions: CD, AD, and TB envisioned the study, developed the concept, and applied for the grant. SA and MK developed the sampling procedures and established the laboratory processes (collection and analyses of the samples) and the data processing. MDA and HTN were responsible for the cost-effectiveness measurement, with support from SB. AS and SM contributed the qualitative study component. MS accounted for the calculations with regard to the random sampling of addresses from the registration offices. LK together with LMH, CD, TR, and TJA designed, developed, and validated the prescreening tool. LB, RB, and M Marx set up the sample shipment logistics. M Meurer, KH, RB, DL, SA, and SO developed data processing pipelines and set up the server. KH developed the questionnaire scanner software. M Meurer, DL, and RB validated the sampling strategy and the sample analysis procedures. PS was responsible for confirmation of positive samples by real-time reverse transcription–polymerase chain reaction. SB registered the trial and was responsible for publishing the study protocol. AD, IM, and SO accessed and verified the data presented in this manuscript and performed the epidemiological analyses. CD performed data linkage with the health authority and supported the sensitivity analyses. AD, MDA, MK, CD, HTN, and SO drafted the manuscript. All authors contributed to the interpretation of the results and manuscript writing and read and approved the final manuscript.Conflicts of Interest: None declared.CONSORT (Consolidated Standards of Reporting Trials) 2010 checklist.Supplementary materials, containing details on trial operationalization and certain calculations as well as supplementary tables and figures.Study presentation, web-based conference on February 8, 2021.