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Author(s): Nicolas Banholzer 1, Kathrin Zürcher 1, Philipp Jent 2, Pascal Bittel 3, Lavinia Furrer 3, Matthias Egger 1,4,5, Tina Hascher 6, Lukas Fenner 1,* 1 Introduction The spread of [...], Background Growing evidence suggests an important contribution of airborne transmission to the overall spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in particular via smaller particles called aerosols. However, the contribution of school children to SARS-CoV-2 transmission remains uncertain. The aim of this study was to assess transmission of airborne respiratory infections and the association with infection control measures in schools using a multiple-measurement approach. Methods and findings We collected epidemiological (cases of Coronavirus Disease 2019 (COVID-19)), environmental (CO.sub.2, aerosol and particle concentrations), and molecular data (bioaerosol and saliva samples) over 7 weeks from January to March 2022 (Omicron wave) in 2 secondary schools (n = 90, average 18 students/classroom) in Switzerland. We analyzed changes in environmental and molecular characteristics between different study conditions (no intervention, mask wearing, air cleaners). Analyses of environmental changes were adjusted for different ventilation, the number of students in class, school and weekday effects. We modeled disease transmission using a semi-mechanistic Bayesian hierarchical model, adjusting for absent students and community transmission. Molecular analysis of saliva (21/262 positive) and airborne samples (10/130) detected SARS-CoV-2 throughout the study (weekly average viral concentration 0.6 copies/L) and occasionally other respiratory viruses. Overall daily average CO.sub.2 levels were 1,064 ± 232 ppm (± standard deviation). Daily average aerosol number concentrations without interventions were 177 ± 109 1/cm.sup.3 and decreased by 69% (95% CrI 42% to 86%) with mask mandates and 39% (95% CrI 4% to 69%) with air cleaners. Compared to no intervention, the transmission risk was lower with mask mandates (adjusted odds ratio 0.19, 95% CrI 0.09 to 0.38) and comparable with air cleaners (1.00, 95% CrI 0.15 to 6.51). Study limitations include possible confounding by period as the number of susceptible students declined over time. Furthermore, airborne detection of pathogens document exposure but not necessarily transmission. Conclusions Molecular detection of airborne and human SARS-CoV-2 indicated sustained transmission in schools. Mask mandates were associated with greater reductions in aerosol concentrations than air cleaners and with lower transmission. Our multiple-measurement approach could be used to continuously monitor transmission risk of respiratory infections and the effectiveness of infection control measures in schools and other congregate settings.