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