Background To accompany the lifting of COVID-19 lockdown measures, Luxembourg implemented a mass screening (MS) programme. The first phase coincided with an early summer epidemic wave in 2020. Methods rRT-PCR-based screening for SARS-CoV-2 was performed by pooling of samples. The infrastructure allowed the testing of the entire resident and cross-border worker populations. The strategy relied on social connectivity within different activity sectors. Invitation frequencies were tactically increased in sectors and regions with higher prevalence. The results were analysed alongside contact tracing data. Findings The voluntary programme covered 49% of the resident and 22% of the cross-border worker populations. It identified 850 index cases with an additional 249 cases from contact tracing. Over-representation was observed in the services, hospitality and construction sectors alongside regional differences. Asymptomatic cases had a significant but lower secondary attack rate when compared to symptomatic individuals. Based on simulations using an agent-based SEIR model, the total number of expected cases would have been 42·9% (90% CI [-0·3, 96·7]) higher without MS. Mandatory participation would have resulted in a further difference of 39·7% [19·6, 59·2]. Interpretation Strategic and tactical MS allows the suppression of epidemic dynamics. Asymptomatic carriers represent a significant risk for transmission. Containment of future outbreaks will depend on early testing in sectors and regions. Higher participation rates must be assured through targeted incentivisation and recurrent invitation. Funding This project was funded by the Luxembourg Ministries of Higher Education and Research, and Health.

The mammalian ubiquitin ligase Hrd1 is the central component of a complex facilitating degradation of misfolded proteins during the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD). Hrd1 associates with cofactors to execute ERAD, but their roles and how they assemble with Hrd1 are not well understood. Here, we identify crucial cofactor interaction domains within Hrd1 and report a previously unrecognised evolutionarily conserved segment within the intrinsically disordered cytoplasmic domain of Hrd1 (termed the HAF-H domain), which engages complementary segments in the cofactors FAM8A1 and Herp (also known as HERPUD1). This domain is required by Hrd1 to interact with both FAM8A1 and Herp, as well as to assemble higher-order Hrd1 complexes. FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery.

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