Post-pandemic respiratory infections in children born during or before the COVID-19 pandemic: a nationwide cohort study in Sweden.

Background: Non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic altered the circulation of respiratory pathogens. Following an initial decline in infections, a resurgence occurred as restrictions eased. We aimed to determine whether reduced early-life exposure to pathogens increased the risk of severe respiratory infections. Methods: In this longitudinal nationwide population-based study in Sweden, we compared a pandemic birth cohort of children born in Sweden between March 1 and December 31 from 2020 (n = 92,791) with aligned pre-pandemic cohorts born between 1 March and December 31 of 2015 (n = 94,552) and of 2018 (n = 96,074). Children with missing covariate data, death, or emigration before the age of two were excluded (10·5%). Baseline characteristics for the first two years of life were summarized. Outcomes were assessed between ages 2-4 years. Hospitalization for overall and specific lower respiratory tract infections (LRTI) was analysed as a binary outcome using logistic regression. Findings: Children born in 2020 had markedly lower hospitalisation rates during their first two years of life than both pre-pandemic cohorts. However, between ages 2 and 4, they exhibited significantly higher hospitalisation risk compared with both pre-pandemic cohorts. Adjusted odds ratio (aOR) for hospitalisation in the 2020 versus 2015 cohort were: all-cause LRTI (2·51 (95% CI 2·26-2·79)), influenza (2·99, 2·38-3·79) and respiratory syncytial virus (RSV) (4·36, 3·60-5·31). Similar patterns were observed for all-cause pneumonia and mycoplasma. The 2018 cohort showed a more mixed pattern, with lower risk for pneumonia but higher risk for RSV. Interpretation: Children born during the COVID-19 pandemic initially had a reduced risk of hospitalisation for respiratory infections, followed by a substantially increased risk in the post-pandemic period compared to children born before the pandemic. These findings suggest that altered early-life microbial exposure due to pandemic-related restrictions may influence subsequent patterns of severe childhood infections through immunological or exposure-related mechanisms and emphasis the need for further research to elucidate underlying mechanisms. Funding: The SCIFI-PEARLS project has basic fundings from the Swedish government and the county councils, the ALF agreement, the Swedish Research Council for Health, Working Life and Welfare, (Forte), and previously a joint grant from Forte-and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas).