Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): study protocol for a two-factorial randomized controlled multi-arm trial with cluster sampling.

To achieve higher effectiveness in population-based SARS-CoV-2 surveillance and to reliably predict the course of an outbreak, screening, and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. This trial implements a two-factorial, randomized, controlled, multi-arm, prospective, interventional, single-blinded design with cluster sampling and four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy based on individuals' self-collection of saliva samples which are then sent to and analyzed by a laboratory. The targeted sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (2500 participants per arm). Strategies differ with respect to tested population groups (individuals vs. all household members) and testing approach (without vs. with pre-screening survey). The trial is complemented by an economic evaluation and qualitative assessment of user experiences. Primary outcomes include costs per completely screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Systems for active surveillance of the general population will gain more importance in the context of pandemics and related disease prevention efforts. The pandemic parameters derived from such active surveillance with routine population monitoring therefore not only enable a prospective assessment of the short-term course of a pandemic, but also a more targeted and thus more effective use of local and short-term countermeasures. ClinicalTrials.gov DRKS00023271 . Registered November 30, 2020, with the German Clinical Trials Register (Deutsches Register Klinischer Studien).

Deckert A ，Anders S ，De Allegri M ，Nguyen HT ，Souares A ，McMahon S ，Meurer M ，Burk R ，Sand M ，Koeppel L ，Hein LM ，Roß T ，Adler T ，Siems T ，Brugnara L ，Brenner S ，Herbst K ，Kirrmaier D ，Duan Y ，Ovchinnikova S ，Boerner K ，Marx M ，Kräusslich HG ，Knop M ，Bärnighausen T ，Denkinger C ... -  《Trials》

Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): a structured summary of a study protocol for a cluster-randomised, two-factorial controlled trial.

Deckert A ，Anders S ，de Allegri M ，Nguyen HT ，Souares A ，McMahon S ，Boerner K ，Meurer M ，Herbst K ，Sand M ，Koeppel L ，Siems T ，Brugnara L ，Brenner S ，Burk R ，Lou D ，Kirrmaier D ，Duan Y ，Ovchinnikova S ，Marx M ，Kräusslich HG ，Knop M ，Bärnighausen T ，Denkinger C ... -  《Trials》

Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

The COVID-19 pandemic is characterized by rapid increases in infection burden owing to the emergence of new variants with higher transmissibility and immune escape. To date, monitoring the COVID-19 pandemic has mainly relied on passive surveillance, yielding biased epidemiological measures owing to the disproportionate number of undetected asymptomatic cases. Active surveillance could provide accurate estimates of the true prevalence to forecast the evolution of the pandemic, enabling evidence-based decision-making. This study compared 4 different approaches of active SARS-CoV-2 surveillance focusing on feasibility and epidemiological outcomes. A 2-factor factorial randomized controlled trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised SARS-CoV-2 prevalence and its precision. The 4 study arms combined 2 factors: individuals versus households and direct testing versus testing conditioned on symptom prescreening. Individuals aged ≥7 years were eligible. Altogether, 27,908 addresses from 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, and a website in 5 languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with reverse transcription loop-mediated isothermal amplification (RT-LAMP); positive and weak results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). Recruitment was conducted between November 18 and December 11, 2020. The response rates in the 4 arms varied between 34.31% (2340/6821) and 41.17% (2043/4962). The prescreening classified 16.61% (1207/7266) of the patients as COVID-19 symptomatic. Altogether, 4232 persons without prescreening and 7623 participating in the prescreening provided 5351 gargle samples, of which 5319 (99.4%) could be analyzed. This yielded 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI 0.14%-0.59%) in the arms without prescreening and 0.05% (95% CI 0.00%-0.108%) in the arms with prescreening (initial contacts only). Specifically, we found a prevalence of 0.31% (95% CI 0.06%-0.58%) for individuals and 0.35% (95% CI 0.09%-0.61%) for households, and lower estimates with prescreening (0.07%, 95% CI 0.0%-0.15% for individuals and 0.02%, 95% CI 0.0%-0.06% for households). Asymptomatic infections occurred in 27% (3/11) of the positive cases with symptom data. The 2 arms without prescreening performed the best regarding effectiveness and accuracy. This study showed that postal mailing of gargle sample kits and returning home-based self-collected liquid gargle samples followed by high-sensitivity RT-LAMP analysis is a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and integration into the public health system may increase the potential to monitor the course of the pandemic. Deutsches Register Klinischer Studien (DRKS) DRKS00023271; https://tinyurl.com/3xenz68a. RR2-10.1186/s13063-021-05619-5.

Deckert A ，Anders S ，Morales I ，De Allegri M ，Nguyen HT ，Souares A ，McMahon S ，Meurer M ，Burk R ，Lou D ，Brugnara L ，Sand M ，Koeppel L ，Maier-Hein L ，Ross T ，Adler TJ ，Brenner S ，Dyer C ，Herbst K ，Ovchinnikova S ，Marx M ，Schnitzler P ，Knop M ，Bärnighausen T ，Denkinger CM ... -  《JMIR Public Health and Surveillance》

Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial.

Emadi A ，Chua JV ，Talwani R ，Bentzen SM ，Baddley J ... -  《Trials》

Comparison of four COVID-19 screening strategies to facilitate early case identification within the homeless shelter population: A structured summary of a study protocol for a randomised controlled trial.

O'Shea T ，Mbuagbaw L ，Mokashi V ，Bulir D ，Gilchrist J ，Smieja N ，Chong S ，Marttala S ，Vera V ，Cvetkovic A ，Smieja M ... -  《Trials》