Reconstructing the impact of COVID-19 on the immunity gap and transmission of respiratory syncytial virus in Lombardy, Italy

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalisation and mortality in young children globally. The social distancing measures implemented against COVID-19 in Lombardy (Italy) disrupted the typically seasonal RSV circulation during 2019-2021 and caused substantially more hospitalisations during 2021-2022. The primary aim of this study is to quantify the immunity gap-defined as the increased proportion of the population naïve to RSV infection following the relaxation of COVID-19 restrictions in Lombardy, which has been hypothesised to be a potential cause of the increased RSV burden in 2021-2022. Methods: We developed a catalytic model to reconstruct changes in the age-dependent susceptibility profile of the Lombardy population throughout the COVID-19 pandemic. The model is calibrated to routinely collected hospitalisation, syndromic, and virological surveillance data and tested for alternative assumptions on age-dependencies in the risk of RSV infection throughout the pandemic. Findings: We estimate that the proportion of the Lombardy population naïve to RSV infection increased by 60.8% (95% CrI: 55.2-65.4%) during the COVID-19 pandemic: from 1.4% (95% CrI: 1.3-1.6%) in 2018-2019 to 2.3% (95% CrI: 2.2-2.5%) before the 2021-2022 season, corresponding to an immunity gap of 0.87% (95% CrI: 0.87-0.88%). We found evidence of heterogeneity in RSV transmission by age, suggesting that the COVID-19 restrictions had variable impact on the contact patterns and risk of RSV infection across ages. Interpretation: We estimate a substantial increase in the population-level susceptibility to RSV in Lombardy during 2019-2021, which contributed to an increase in primary RSV infections in 2021-2022. Funding: UK Medical Research Council (MRC), UK Foreign, Commonwealth & Development Office (FCDO), EDCTP2 programme, European Union, Wellcome Trust, Royal Society, EU-MUR PNRR INF-ACT.