Nightlife and low immunity drove transmission of SARS-CoV-2 gamma in Luxembourg, 2021.

In summer 2021, while the Delta variant was predominant in many European countries, Luxembourg experienced a large outbreak of the P.1.17.1 SARS-CoV-2 Gamma variant. This surge coincided with the introduction of digital COVID-19 certificates and eased restrictions prior to national holiday festivities. We investigated the molecular and epidemiological factors contributing to SARS-CoV-2 Gamma transmission. All laboratory SARS-CoV-2 confirmed cases were interviewed by contact tracing teams on exposures at nightlife venues, family gatherings, schools, and workplaces. Gamma sublineages were investigated through environmental wastewater surveillance, in addition to whole genome sequencing of clinical data. Infection clusters were analysed combining phylogenetic with epidemiological exposures. From June 22 to August 12, 2021, we identified 1,049 cases of the Gamma P.1.17.1 sublineage, representing 39.2% of all sequenced cases. Initially, nightlife was the most frequent source setting (49.1%) with young adults accounting for 92.3% of these cases. Later, transmission shifted towards family (30.4%) setting with a corresponding increase in the age distribution. The C26645T mutation in the M-protein was associated with attending specific nightclub venues. Notably, 96.8% of cases were in unvaccinated individuals, and while P.1.17.1 was also detected in neighboring countries, 75.6% of the sequences submitted to GISAID were from Luxembourg. The study suggests the role of nightlife and low population immunity in driving the summer surge of SARS-CoV-2 among young adults, with digital certificates showing minimal impact on transmission. Sequencing of clinical and wastewater samples in combination with contact tracing was crucial to inform the outbreak investigation.