| Summary: | Background: During COVID-19 pandemic, school closure has been mandated in analogy to its effect against influenza, but it is unclear whether schools are early COVID-19 amplifiers. Methods: We performed a cross-sectional and prospective cohort study in Italy during the second COVID-19 wave (from September 30, 2020 until at least February 28, 2021). We used databases from the Italian Ministry of Education, the Veneto region systems of SARS-CoV-2 cases notification and of schools’ secondary cases tracing to compare SARS-CoV-2 incidence in students/school staff and general population and incidence across age groups. Number of tests, secondary infections by type of index case and ratio cases/ tests per school were estimated using an adjusted multivariable generalized linear regression model. Regional reproduction numbers Rt were estimated from Italian Civil Protection daily incidence data with a method of posterior distribution using a Markov Chain Monte Carlo algorithm. Findings: SARS-CoV-2 incidence among students was lower than in the general population. Secondary infections at school were <1%, and clusters of ≥2 secondary cases occurred in 5–7% of the analysed schools. Incidence among teachers was comparable to the population of similar age (P = 0.23). Secondary infections among teachers were rare, occurring more frequently when the index case was a teacher than a student (37% vs. 10%, P = 0.007). Before and around the date of school opening in Veneto, SARS-CoV-2 incidence grew maximally in 20–29- and 45–49-years old individuals, not among students. The lag between school opening dates in Italian regions and the increase in the regional COVID-19 Rt was not uniform. Finally, school closures in two regions where they were implemented before other measures did not affect Rt decrease. Interpretation: This analysis does not support a role for school opening as a driver of the second COVID-19 wave in Italy, a large European country with high SARS-CoV-2 incidence. Funding: Fondazione MITE.
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