Excess mortality during the COVID-19 outbreak in Italy: a two-stage interrupted time series analysis

Background: Italy was the first country outside China to experience the impact of the COVID-19 pandemic, which resulted in a significant health burden. This study presents an analysis of the excess mortality across the 107 Italian provinces, stratified by sex, age group, and period of the outbreak. Methods: The analysis was performed using a two-stage interrupted time series design using daily mortality data for the period January 2015 - May 2020. In the first stage, we performed province-level quasi-Poisson regression models, with smooth functions to define a baseline risk while accounting for trends and weather conditions and to flexibly estimate the variation in excess risk during the outbreak. Estimates were pooled in the second stage using a mixed-effects multivariate meta-analysis. Results: In the period 15 February - 15 May 2020, we estimated an excess of 47,490 (95% empirical confidence intervals: 43,984 to 50,362) deaths in Italy, corresponding to an increase of 29.5% (95%eCI: 26.8 to 31.9%) from the expected mortality. The analysis indicates a strong geographical pattern, with the majority of excess deaths occurring in northern regions, where few provinces experienced up to 800% increase during the peak in late March. There were differences by sex, age, and area both in the overall impact and in its temporal distribution. Conclusions: This study offers a detailed picture of excess mortality during the first months of the COVID-19 pandemic in Italy. The strong geographical and temporal patterns can be related to implementation of lockdown policies and multiple direct and indirect pathways in mortality risk.